CXCR receptors with specificity for CXCL12 CHEMOKINE. The receptors may play a role in HEMATOPOIESIS regulation and can also function as coreceptors for the HUMAN IMMUNODEFICIENCY VIRUS.
CXCR receptors that are expressed on the surface of a number of cell types, including T-LYMPHOCYTES; NK CELLS; DENDRITIC CELLS; and a subset of B-LYMPHOCYTES. The receptors are activated by CHEMOKINE CXCL9; CHEMOKINE CXCL10; and CHEMOKINE CXCL11.
Chemokine receptors that are specific for CXC CHEMOKINES.
A CXC chemokine that is chemotactic for T-LYMPHOCYTES and MONOCYTES. It has specificity for CXCR4 RECEPTORS. Two isoforms of CXCL12 are produced by alternative mRNA splicing.
CXCR receptors isolated initially from BURKITT LYMPHOMA cells. CXCR5 receptors are expressed on mature, recirculating B-LYMPHOCYTES and are specific for CHEMOKINE CXCL13.
High-affinity G-protein-coupled receptors for INTERLEUKIN-8 present on NEUTROPHILS; MONOCYTES; and T-LYMPHOCYTES. These receptors also bind several other CXC CHEMOKINES.
Group of chemokines with paired cysteines separated by a different amino acid. CXC chemokines are chemoattractants for neutrophils but not monocytes.
High-affinity G-protein-coupled receptors for INTERLEUKIN-8 present on NEUTROPHILS; MONOCYTES; and BASOPHILS.
Ring compounds having atoms other than carbon in their nuclei. (Grant & Hackh's Chemical Dictionary, 5th ed)
Cell surface glycoproteins that bind to chemokines and thus mediate the migration of pro-inflammatory molecules. The receptors are members of the seven-transmembrane G protein-coupled receptor family. Like the CHEMOKINES themselves, the receptors can be divided into at least three structural branches: CR, CCR, and CXCR, according to variations in a shared cysteine motif.
A CXC chemokine that is induced by GAMMA-INTERFERON. It is a chemotactic factor for activated T-LYMPHOCYTES and has specificity for the CXCR3 RECEPTOR.
A CXC chemokine that is induced by GAMMA-INTERFERON and is chemotactic for MONOCYTES and T-LYMPHOCYTES. It has specificity for the CXCR3 RECEPTOR.
An INTEFERON-inducible CXC chemokine that is specific for the CXCR3 RECEPTOR.
The movement of cells or organisms toward or away from a substance in response to its concentration gradient.
A CXC chemokine that has stimulatory and chemotactic activities towards NEUTROPHILS. It has specificity for CXCR1 RECEPTORS and CXCR2 RECEPTORS.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
A CXC chemokine with specificity for CXCR2 RECEPTORS. It has growth factor activities and is implicated as a oncogenic factor in several tumor types.
The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.
A CXC chemokine that is chemotactic for B-LYMPHOCYTES. It has specificity for CXCR5 RECEPTORS.
Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C; (CHEMOKINES, C); CC; (CHEMOKINES, CC); and CXC; (CHEMOKINES, CXC); according to variations in a shared cysteine motif.
A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
CCR receptors with specificity for CHEMOKINE CCL19 and CHEMOKINE CCL21. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
CCR receptors with specificity for CHEMOKINE CCL17 and CHEMOKINE CCL22. They are expressed at high levels in T-LYMPHOCYTES; MAST CELLS; DENDRITIC CELLS; and NK CELLS.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Benign epidermal proliferations or tumors; some are viral in origin.
A cell line derived from cultured tumor cells.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Cellular receptors that bind the human immunodeficiency virus that causes AIDS. Included are CD4 ANTIGENS, found on T4 lymphocytes, and monocytes/macrophages, which bind to the HIV ENVELOPE PROTEIN GP120.
Cell surface proteins that bind cytokines and trigger intracellular changes influencing the behavior of cells.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
CCR receptors with specificity for CHEMOKINE CCL3; CHEMOKINE CCL4; and CHEMOKINE CCL5. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; MACROPHAGES; MAST CELLS; and NK CELLS. The CCR5 receptor is used by the HUMAN IMMUNODEFICIENCY VIRUS to infect cells.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Established cell cultures that have the potential to propagate indefinitely.
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
A CXC chemokine that is predominantly expressed in EPITHELIAL CELLS. It has specificity for the CXCR2 RECEPTORS and is involved in the recruitment and activation of NEUTROPHILS.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.
A large group of structurally diverse cell surface receptors that mediate endocytic uptake of modified LIPOPROTEINS. Scavenger receptors are expressed by MYELOID CELLS and some ENDOTHELIAL CELLS, and were originally characterized based on their ability to bind acetylated LOW-DENSITY LIPOPROTEINS. They can also bind a variety of other polyanionic ligand. Certain scavenger receptors can internalize micro-organisms as well as apoptotic cells.
A species of LENTIVIRUS, subgenus feline lentiviruses (LENTIVIRUSES, FELINE) isolated from cats with a chronic wasting syndrome, presumed to be immune deficiency. There are 3 strains: Petaluma (FIP-P), Oma (FIP-O) and Puma lentivirus (PLV). There is no antigenic relationship between FIV and HIV, nor does FIV grow in human T-cells.
External envelope protein of the human immunodeficiency virus which is encoded by the HIV env gene. It has a molecular weight of 120 kDa and contains numerous glycosylation sites. Gp120 binds to cells expressing CD4 cell-surface antigens, most notably T4-lymphocytes and monocytes/macrophages. Gp120 has been shown to interfere with the normal function of CD4 and is at least partly responsible for the cytopathic effect of HIV.
Aquatic vertebrate sensory system in fish and amphibians. It is composed of sense organs (canal organs and pit organs) containing neuromasts (MECHANORECEPTORS) that detect water displacement caused by moving objects.
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
Regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors.
Ability of neoplasms to infiltrate and actively destroy surrounding tissue.
A CXC chemokine that is synthesized by activated MONOCYTES and NEUTROPHILS. It has specificity for CXCR2 RECEPTORS.
Chemical substances that attract or repel cells. The concept denotes especially those factors released as a result of tissue injury, microbial invasion, or immunologic activity, that attract LEUKOCYTES; MACROPHAGES; or other cells to the site of infection or insult.
Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.
The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions.
A CC-type chemokine with specificity for CCR7 RECEPTORS. It has activity towards DENDRITIC CELLS and T-LYMPHOCYTES.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
Inbred BALB/c mice are a strain of laboratory mice that have been selectively bred to be genetically identical to each other, making them useful for scientific research and experiments due to their consistent genetic background and predictable responses to various stimuli or treatments.
The simultaneous or sequential binding of multiple cell surface receptors to different ligands resulting in coordinated stimulation or suppression of signal transduction.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.
Adherence of cells to surfaces or to other cells.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Group of chemokines with adjacent cysteines that are chemoattractants for lymphocytes, monocytes, eosinophils, basophils but not neutrophils.
Specific molecular components of the cell capable of recognizing and interacting with a virus, and which, after binding it, are capable of generating some signal that initiates the chain of events leading to the biological response.
A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.
Cell surface proteins that bind interleukins and trigger intracellular changes influencing the behavior of cells.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Progenitor cells from which all blood cells derive.
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
Proteins obtained from the ZEBRAFISH. Many of the proteins in this species have been the subject of studies involving basic embryological development (EMBRYOLOGY).
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.
Cell separation is the process of isolating and distinguishing specific cell types or individual cells from a heterogeneous mixture, often through the use of physical or biological techniques.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
The release of stem cells from the bone marrow into the peripheral blood circulation for the purpose of leukapheresis, prior to stem cell transplantation. Hematopoietic growth factors or chemotherapeutic agents often are used to stimulate the mobilization.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.
A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.

Phenotypic and functional evidence for the expression of CXCR4 receptor during megakaryocytopoiesis. (1/2860)

The identification of stromal cell-derived factor (SDF)-1alpha as a chemoattractant for human progenitor cells suggests that this chemokine and its receptor might represent critical determinants for the homing, retention, and exit of precursor cells from hematopoietic organs. In this study, we investigated the expression profile of CXCR4 receptor and the biological activity of SDF-1alpha during megakaryocytopoiesis. CD34(+) cells from bone marrow and cord blood were purified and induced to differentiate toward the megakaryocyte lineage by a combination of stem-cell factor (SCF) and recombinant human pegylated megakaryocyte growth and development factor (PEG-rhuMGDF). After 6 days of culture, a time where mature and immature megakaryocytes were present, CD41(+) cells were immunopurified and CXCR4mRNA expression was studied. High transcript levels were detected by a RNase protection assay in cultured megakaryocytes derived from cord blood CD34(+) cells as well as in peripheral blood platelets. The transcript levels were about equivalent to that found in activated T cells. By flow cytometry, a large fraction (ranging from 30% to 100%) of CD41(+) cells showed high levels of CXCR4 antigen on their surface, its expression increasing in parallel with the CD41 antigen during megakaryocytic differentiation. CXCR4 protein was also detected on peripheral blood platelets. SDF-1alpha acts on megakaryocytes by inducing intracellular calcium mobilization and actin polymerization. In addition, in in vitro transmigration experiments, a significant proportion of megakaryocytes was observed to respond to this chemokine. This cell migration was inhibited by pertussis toxin, indicating coupling of this signal to heterotrimeric guanine nucleotide binding proteins. Although a close correlation between CD41a and CXCR4 expession was observed, cell surface markers as well as morphological criteria indicate a preferential attraction of immature megakaryocytes (low level of CD41a and CD42a), suggesting that SDF-1alpha is a potent attractant for immature megakaryocytic cells but is less active on fully mature megakaryocytes. This hypothesis was further supported by the observation that SDF-1alpha induced the migration of colony forming unit-megakaryocyte progenitors (CFU-MK) and the expression of activation-dependent P-selectin (CD62P) surface antigen on early megakaryocytes, although no effect was observed on mature megakaryocytes and platelets. These results indicate that CXCR4 is expressed by human megakaryocytes and platelets. Furthermore, based on the lower responses of mature megakaryocytes and platelets to SDF-1alpha as compared with early precursors, these data suggest a role for this chemokine in the maintenance and homing during early stages of megakaryocyte development. Moreover, because megakaryocytes are also reported to express CD4, it becomes important to reevaluate the role of direct infection of these cells by the human immunodeficiency virus (HIV)-1 in HIV-1-related thrombocytopenia.  (+info)

Interactions between Tat and TAR and human immunodeficiency virus replication are facilitated by human cyclin T1 but not cyclins T2a or T2b. (2/2860)

The transcriptional transactivator (Tat) from the human immunodeficiency virus (HIV) does not function efficiently in Chinese hamster ovary (CHO) cells. Only somatic cell hybrids between CHO and human cells and CHO cells containing human chromosome 12 (CHO12) support high levels of Tat transactivation. This restriction was mapped to interactions between Tat and TAR. Recently, human cyclin T1 was found to increase the binding of Tat to TAR and levels of Tat transactivation in rodent cells. By combining individually with CDK9, cyclin T1 or related cyclins T2a and T2b form distinct positive transcription elongation factor b (P-TEFb) complexes. In this report, we found that of these three cyclins, only cyclin T1 is encoded on human chromosome 12 and is responsible for its effects in CHO cells. Moreover, only human cyclin T1, not mouse cyclin T1 or human cyclins T2a or T2b, supported interactions between Tat and TAR in vitro. Finally, after introducing appropriate receptors and human cyclin T1 into CHO cells, they became permissive for infection by and replication of HIV.  (+info)

Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. (3/2860)

To define predictors of survival time in late human immunodeficiency virus type 1 (HIV-1) disease, long- and short-duration survivors were studied after their CD4+ T cells fell to +info)

Effect of mutations in the second extracellular loop of CXCR4 on its utilization by human and feline immunodeficiency viruses. (4/2860)

CCR5 and CXCR4 are the principal CD4-associated coreceptors used by human immunodeficiency virus type 1 (HIV-1). CXCR4 is also a receptor for the feline immunodeficiency virus (FIV). The rat CXCR4 cannot mediate infection by HIV-1NDK or by FIVPET (both cell line-adapted strains) because of sequence differences with human CXCR4 in the second extracellular loop (ECL2). Here we made similar observations for HIV-189.6 (a strain also using CCR5) and for a primary HIV-1 isolate. It showed the role of ECL2 in the coreceptor activity of CXCR4 for different types of HIV-1 strains. By exchanging ECL2 residues between human and rat CXCR4, we found that several amino acid differences contributed to the inactivity of the rat CXCR4 toward HIV-189.6. In contrast, its inactivity toward HIV-1NDK seemed principally due to a serine at position 193 instead of to an aspartic acid (Asp193) in human CXCR4. Likewise, a mutation of Asp187 prevented usage of CXCR4 by FIVPET. Different mutations of Asp193, including its replacement by a glutamic acid, markedly reduced or suppressed the activity of CXCR4 for HIV-1NDK infection, indicating that the negative charge was not the only requirement. Mutations of Asp193 and of arginine residues (Arg183 and Arg188) of CXCR4 reduced the efficiency of HIV-1 infection for all HIV-1 strains tested. Other ECL2 mutations tested had strain-specific effects or no apparent effect on HIV-1 infection. The ECL2 mutants allowed us to identify residues contributing to the epitope of the 12G5 monoclonal antibody. Overall, residues with different charges and interspersed in ECL2 seem to participate in the coreceptor activity of CXCR4. This suggests that a conformational rather than linear epitope of ECL2 contributes to the HIV-1 binding site. However, certain HIV-1 and FIV strains seem to require the presence of a particular ECL2 residue.  (+info)

Identification of CXCR4 domains that support coreceptor and chemokine receptor functions. (5/2860)

The interaction of the chemokine stromal cell-derived factor 1 (SDF-1) with its receptor CXCR4 is vital for cell trafficking during development, is capable of inhibiting human immunodeficiency virus type 1 (HIV-1) utilization of CXCR4 as a coreceptor, and has been implicated in delaying disease progression to AIDS in vivo. Because of the importance of this chemokine-chemokine receptor pair to both development and disease, we investigated the molecular basis of the interaction between CXCR4 and its ligands SDF-1 and HIV-1 envelope. Using CXCR4 chimeras and mutants, we determined that SDF-1 requires the CXCR4 amino terminus for binding and activates downstream signaling pathways by interacting with the second extracellular loop of CXCR4. SDF-1-mediated activation of CXCR4 required the Asp-Arg-Tyr motif in the second intracellular loop of CXCR4, was pertussis toxin sensitive, and did not require the distal C-terminal tail of CXCR4. Several CXCR4 mutants that were not capable of binding SDF-1 or signaling still supported HIV-1 infection, indicating that the ability of CXCR4 to function as a coreceptor is independent of its ability to signal. Direct binding studies using the X4 gp120s HXB, BH8, and MN demonstrated the ability of HIV-1 gp120 to bind directly and specifically to the chemokine receptor CXCR4 in a CD4-dependent manner, using a conformationally complex structure on CXCR4. Several CXCR4 variants that did not support binding of soluble gp120 could still function as viral coreceptors, indicating that detectable binding of monomeric gp120 is not always predictive of coreceptor function.  (+info)

Will multiple coreceptors need to be targeted by inhibitors of human immunodeficiency virus type 1 entry? (6/2860)

Despite being able to use the Bonzo coreceptor as efficiently as CCR5 in transfected cells, pediatric human immunodeficiency virus type 1 isolate P6 was unable to replicate in peripheral blood mononuclear cells (PBMC) lacking the CCR5 receptor. Furthermore, its replication in wild-type PBMC was completely inhibited by inhibitors of CCR5-mediated entry. Similarly, maternal isolate M6 could use CCR5, CXCR4, Bonzo, and other coreceptors in transfected cells but was completely sensitive to inhibitors of CCR5- and CXCR4-mediated entry when grown in PBMC. The ability of these viruses to use coreceptors in addition to CCR5 and CXCR4 in vitro was, therefore, irrelevant to their drug sensitivity in primary cells. We argue that CCR5 and CXCR4 should remain the primary targets for antiviral drug development, pending strong evidence to the contrary.  (+info)

Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry. (7/2860)

Chemokine receptors and related seven-transmembrane-segment (7TMS) receptors serve as coreceptors for entry of human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIV) into target cells. Each of these otherwise diverse coreceptors contains an N-terminal region that is acidic and tyrosine rich. Here, we show that the chemokine receptor CCR5, a principal HIV-1 coreceptor, is posttranslationally modified by O-linked glycosylation and by sulfation of its N-terminal tyrosines. Sulfated tyrosines contribute to the binding of CCR5 to MIP-1 alpha, MIP-1 beta, and HIV-1 gp120/CD4 complexes and to the ability of HIV-1 to enter cells expressing CCR5 and CD4. CXCR4, another important HIV-1 coreceptor, is also sulfated. Tyrosine sulfation may contribute to the natural function of many 7TMS receptors and may be a modification common to primate immunodeficiency virus coreceptors.  (+info)

Cofactors for human immunodeficiency virus entry into primary macrophages. (8/2860)

Macrophages are permissive for macrophage-tropic (M-tropic) human immunodeficiency virus type 1 (HIV-1) isolates that use CCR5 for entry but are resistant to CXCR-4-dependent T cell-tropic prototype strains. M-tropic variants are critical for HIV-1 transmission, and persons who are homozygous for an inactivating mutation of CCR5 are resistant to HIV-1 in vivo. In vitro, their macrophages and lymphocytes are resistant to M-tropic strains that depend on CCR5. It is shown that CCR5-deficient macrophages are permissive for a dual-tropic isolate, 89.6, that uses CCR5, CXCR-4, and other cofactors. Entry by 89.6 into CCR5-deficient macrophages was blocked by the CXCR-4 ligand SDF and by an anti-CXCR-4 antibody. Immunoflorescence staining and reverse transcription PCR confirmed macrophage CXCR-4 expression. Thus, CXCR-4 on macrophages mediates entry of certain dual-tropic but not T cell-tropic isolates. Therefore, HIV-1 strains differ in how they utilize chemokine receptors as cofactors for entry, and the ability of a chemokine receptor to facilitate entry depends on the cell in which it is expressed.  (+info)

C-X-C chemokine receptor type 4 (CXCR4) is a type of protein found on the surface of some cells, including white blood cells, and is a type of G protein-coupled receptor (GPCR). CXCR4 binds specifically to the chemokine ligand CXCL12 (also known as stromal cell-derived factor 1, or SDF-1), which plays a crucial role in the trafficking and homing of immune cells, particularly hematopoietic stem cells and lymphocytes. The binding of CXCL12 to CXCR4 triggers various intracellular signaling pathways that regulate cell migration, proliferation, survival, and differentiation.

In addition to its role in the immune system, CXCR4 has been implicated in several physiological and pathological processes, such as embryonic development, neurogenesis, angiogenesis, cancer metastasis, and HIV infection. In cancer, the overexpression of CXCR4 or increased levels of its ligand CXCL12 have been associated with poor prognosis, tumor growth, and metastasis in various types of malignancies, including breast, lung, prostate, colon, and ovarian cancers. In HIV infection, the CXCR4 coreceptor, together with CD4, facilitates viral entry into host cells, particularly during the later stages of the disease when the virus shifts its preference from CCR5 to CXCR4 as a coreceptor.

In summary, CXCR4 is a cell-surface receptor that binds specifically to the chemokine ligand CXCL12 and plays essential roles in immune cell trafficking, hematopoiesis, cancer metastasis, and HIV infection.

CXCR3 is a type of chemokine receptor that is primarily expressed on the surface of certain immune cells, including T lymphocytes (a type of white blood cell involved in immune response). It belongs to the Class A orphan G protein-coupled receptors family.

CXCR3 has three known subtypes, CXCR3-A, CXCR3-B, and CXCR3-C, each with different roles in regulating immune cell functions. These receptors bind to specific chemokines, which are small signaling proteins that help direct the movement of immune cells towards sites of inflammation or infection.

The chemokines that bind to CXCR3 include CXCL9, CXCL10, and CXCL11, which are produced by various cell types in response to inflammation or injury. Once bound to these chemokines, CXCR3 activates intracellular signaling pathways that trigger a range of responses, such as cell migration, activation, and proliferation.

In the context of disease, CXCR3 has been implicated in various pathological conditions, including cancer, autoimmune diseases, and viral infections, due to its role in regulating immune cell trafficking and activation.

CXCR (C-X-C chemokine receptor) is a type of G protein-coupled receptor that binds to certain chemokines, which are small signaling proteins involved in immunity and inflammation. Specifically, CXCR receptors bind to C-X-C chemokines, a subfamily of chemokines characterized by the presence of three amino acids (X) between two conserved cysteine residues.

The CXCR family includes several members, such as CXCR1, CXCR2, CXCR3, CXCR4, and CXCR5, among others. These receptors play crucial roles in various physiological processes, including the recruitment of immune cells to sites of infection or injury, hematopoiesis, angiogenesis, and cancer metastasis.

One of the most well-studied members of this family is CXCR4, which binds to the chemokine CXCL12 (also known as stromal cell-derived factor 1 or SDF-1). The CXCR4/CXCL12 axis has been implicated in several diseases, including HIV infection, cancer, and inflammatory disorders.

In summary, CXCR receptors are a group of G protein-coupled receptors that bind to C-X-C chemokines, playing essential roles in immunity, inflammation, and other physiological processes.

Chemokine (C-X-C motif) ligand 12 (CXCL12), also known as stromal cell-derived factor 1 (SDF-1), is a small signaling protein belonging to the chemokine family. Chemokines are a group of cytokines, or signaling molecules, that play important roles in immune responses and inflammation by recruiting and activating various immune cells.

CXCL12 is produced by several types of cells, including stromal cells, endothelial cells, and certain immune cells. It exerts its effects by binding to a specific receptor called C-X-C chemokine receptor type 4 (CXCR4), which is found on the surface of various cell types, including immune cells, stem cells, and some cancer cells.

The CXCL12-CXCR4 axis plays crucial roles in various physiological processes, such as embryonic development, tissue homeostasis, hematopoiesis (the formation of blood cells), and neurogenesis (the formation of neurons). Additionally, this signaling pathway has been implicated in several pathological conditions, including cancer metastasis, inflammatory diseases, and HIV infection.

In summary, Chemokine CXCL12 is a small signaling protein that binds to the CXCR4 receptor and plays essential roles in various physiological processes and pathological conditions.

CXCR5 is a type of chemokine receptor that is primarily expressed on the surface of certain immune cells, including B cells and some T cells. It belongs to the family of G protein-coupled receptors (GPCRs) and plays a crucial role in the trafficking and homing of these immune cells to specific tissues in the body.

CXCR5 specifically binds to a chemokine ligand called CXCL13, which is produced by various cell types, including stromal cells in lymphoid organs. The binding of CXCL13 to CXCR5 triggers a signaling cascade that leads to the activation of several downstream signaling pathways, ultimately resulting in the migration and accumulation of immune cells in the vicinity of the CXCL13 source.

In the context of the immune system, CXCR5 is essential for the formation of germinal centers, which are specialized structures within lymphoid organs where B cells undergo activation, proliferation, and differentiation into antibody-secreting plasma cells. The interaction between CXCL13 and CXCR5 helps to recruit B cells and follicular T helper (Tfh) cells to the germinal center, where they can engage in productive interactions that drive humoral immune responses.

Abnormalities in CXCR5 signaling have been implicated in various pathological conditions, including autoimmune diseases, cancer, and infectious diseases. Therefore, understanding the molecular mechanisms underlying CXCR5 function is of great interest for the development of novel therapeutic strategies to target these disorders.

Interleukin-8 (IL-8) receptors are a type of G protein-coupled receptor that bind to and are activated by the cytokine IL-8. There are two main types of IL-8 receptors, known as CXCR1 and CXCR2.

IL-8B, also known as CXCR2, is a gene that encodes for the Interleukin-8 receptor B. This receptor is found on the surface of various cells, including neutrophils, monocytes, and endothelial cells. It plays a crucial role in the immune response, particularly in the recruitment and activation of neutrophils to sites of infection or inflammation.

IL-8B has a high affinity for IL-8 and other related chemokines, such as CXCL1, CXCL5, and CXCL7. Upon binding to its ligand, IL-8B activates various signaling pathways that lead to the mobilization and migration of neutrophils towards the site of inflammation. This process is critical for the elimination of invading pathogens and the resolution of inflammation.

However, excessive or prolonged activation of IL-8B has been implicated in various pathological conditions, including chronic inflammation, cancer, and autoimmune diseases. Therefore, targeting IL-8B with therapeutic agents has emerged as a promising strategy for the treatment of these conditions.

Chemokines are a family of small signaling proteins that are involved in immune regulation and inflammation. They mediate their effects by interacting with specific cell surface receptors, leading to the activation and migration of various types of immune cells. Chemokines can be divided into four subfamilies based on the arrangement of conserved cysteine residues near the N-terminus: CXC, CC, C, and CX3C.

CXC chemokines are characterized by the presence of a single amino acid (X) between the first two conserved cysteine residues. They play important roles in the recruitment and activation of neutrophils, which are critical effector cells in the early stages of inflammation. CXC chemokines can be further divided into two subgroups based on the presence or absence of a specific amino acid sequence (ELR motif) near the N-terminus: ELR+ and ELR-.

ELR+ CXC chemokines, such as IL-8, are potent chemoattractants for neutrophils and play important roles in the recruitment of these cells to sites of infection or injury. They bind to and activate the CXCR1 and CXCR2 receptors on the surface of neutrophils, leading to their migration towards the source of the chemokine.

ELR- CXC chemokines, such as IP-10 and MIG, are involved in the recruitment of T cells and other immune cells to sites of inflammation. They bind to and activate different receptors, such as CXCR3, on the surface of these cells, leading to their migration towards the source of the chemokine.

Overall, CXC chemokines play important roles in the regulation of immune responses and inflammation, and dysregulation of their expression or activity has been implicated in a variety of diseases, including cancer, autoimmune disorders, and infectious diseases.

Interleukin-8 (IL-8) receptors are a type of cell surface receptor that bind to and are activated by the cytokine IL-8. There are two main types of IL-8 receptors, known as CXCR1 and CXCR2. Both of these receptors belong to the G protein-coupled receptor (GPCR) family and play important roles in the immune response, particularly in the recruitment and activation of neutrophils, a type of white blood cell that helps to fight infection.

IL-8A, also known as CXCR1, is a specific subtype of IL-8 receptor. It is a 354-amino acid protein that is expressed on the surface of many different types of cells, including neutrophils, monocytes, and certain tumor cells. When IL-8 binds to CXCR1, it activates a variety of signaling pathways within the cell that lead to changes in gene expression, cell activation, and chemotaxis (directed movement) towards the source of IL-8.

CXCR1 plays an important role in the immune response to bacterial and fungal infections, as well as in the development and progression of certain inflammatory diseases and cancers. It is also a target for drug development, particularly in the areas of cancer therapy and inflammatory disease.

Heterocyclic compounds are organic compounds that contain at least one atom within the ring structure, other than carbon, such as nitrogen, oxygen, sulfur or phosphorus. These compounds make up a large class of naturally occurring and synthetic materials, including many drugs, pigments, vitamins, and antibiotics. The presence of the heteroatom in the ring can have significant effects on the physical and chemical properties of the compound, such as its reactivity, stability, and bonding characteristics. Examples of heterocyclic compounds include pyridine, pyrimidine, and furan.

Chemokine receptors are a type of G protein-coupled receptor (GPCR) that bind to chemokines, which are small signaling proteins involved in immune cell trafficking and inflammation. These receptors play a crucial role in the regulation of immune responses, hematopoiesis, and development. Chemokine receptors are expressed on the surface of various cells, including leukocytes, endothelial cells, and fibroblasts. Upon binding to their respective chemokines, these receptors activate intracellular signaling pathways that lead to cell migration, activation, or proliferation. There are several subfamilies of chemokine receptors, including CXCR, CCR, CX3CR, and XCR, each with distinct specificities for different chemokines. Dysregulation of chemokine receptor signaling has been implicated in various pathological conditions, such as autoimmune diseases, cancer, and viral infections.

Chemokine (C-X-C motif) ligand 11 (CXCL11) is a small cytokine protein that belongs to the chemokine family, which are chemotactic cytokines involved in immune cell trafficking and inflammation. CXCL11 specifically binds to the CXCR3 receptor found on the surface of certain immune cells, including T lymphocytes and natural killer (NK) cells, and plays a role in their recruitment to sites of infection or injury.

CXCL11 is produced by various cell types, including monocytes, endothelial cells, and fibroblasts, in response to pro-inflammatory signals such as interferon-gamma (IFN-γ). It has been shown to have potent chemoattractant properties for Th1 lymphocytes and NK cells, contributing to the development of cell-mediated immune responses. Additionally, CXCL11 has been implicated in several physiological and pathological processes, including angiogenesis, tumorigenesis, and autoimmune diseases.

Chemokine (C-X-C motif) ligand 10 (CXCL10), also known as interferon-gamma-inducible protein 10 (IP-10), is a small cytokine protein that belongs to the chemokine family. Chemokines are a group of signaling proteins that play crucial roles in immune responses and inflammation by recruiting various immune cells to the sites of infection or injury.

CXCL10 is primarily produced by several cell types, including monocytes, endothelial cells, and fibroblasts, in response to stimulation by interferon-gamma (IFN-γ), a cytokine that is critical for the activation of immune cells during an immune response. CXCL10 specifically binds to and activates its receptor, CXCR3, which is expressed on various immune cells such as T lymphocytes, natural killer (NK) cells, and monocytes.

The binding of CXCL10 to CXCR3 triggers a cascade of intracellular signaling events that result in the activation and migration of these immune cells towards the site of inflammation or infection. Consequently, CXCL10 plays essential roles in various physiological and pathological processes, including the recruitment of immune cells to sites of viral infections, tumor growth, and autoimmune diseases.

In summary, Chemokine CXCL10 is a crucial signaling protein that mediates immune cell trafficking and activation during inflammation and immune responses.

Chemokine (C-X-C motif) ligand 9 (CXCL9), also known as monokine induced by interferon-gamma (MIG), is a small protein that belongs to the chemokine family. Chemokines are a group of signaling proteins that play crucial roles in immune responses, including attracting and activating specific types of immune cells to sites of infection or inflammation.

CXCL9 is primarily produced by various cell types, such as monocytes, endothelial cells, and fibroblasts, upon stimulation with interferon-gamma (IFN-γ). This chemokine specifically binds to the C-X-C motif receptor 3 (CXCR3) on the surface of various immune cells, such as T lymphocytes, natural killer (NK) cells, and monocytes.

The primary function of CXCL9 is to recruit and activate these immune cells to areas where it is expressed, which typically occurs in response to infection or tissue damage. By attracting and activating these immune cells, CXCL9 helps to orchestrate the immune response against pathogens and contributes to the resolution of inflammation. Dysregulation of CXCL9 expression has been implicated in various diseases, including autoimmune disorders, chronic inflammatory conditions, and cancer.

Chemotaxis is a term used in biology and medicine to describe the movement of an organism or cell towards or away from a chemical stimulus. This process plays a crucial role in various biological phenomena, including immune responses, wound healing, and the development and progression of diseases such as cancer.

In chemotaxis, cells can detect and respond to changes in the concentration of specific chemicals, known as chemoattractants or chemorepellents, in their environment. These chemicals bind to receptors on the cell surface, triggering a series of intracellular signaling events that ultimately lead to changes in the cytoskeleton and directed movement of the cell towards or away from the chemical gradient.

For example, during an immune response, white blood cells called neutrophils use chemotaxis to migrate towards sites of infection or inflammation, where they can attack and destroy invading pathogens. Similarly, cancer cells can use chemotaxis to migrate towards blood vessels and metastasize to other parts of the body.

Understanding chemotaxis is important for developing new therapies and treatments for a variety of diseases, including cancer, infectious diseases, and inflammatory disorders.

Chemokine CXCL6 is a type of small signaling protein that belongs to the CXC chemokine family. Its primary function is to attract and guide the movement (chemotaxis) of specific types of immune cells, such as neutrophils, to sites of inflammation or infection in the body.

CXCL6 is also known as granulocyte chemotactic protein 2 (GCP-2) and is produced by various cell types, including monocytes, macrophages, endothelial cells, and fibroblasts. It binds to and activates the CXCR1 and CXCR2 receptors found on the surface of neutrophils, which triggers a series of intracellular signaling events that lead to the migration of these cells towards the source of the chemokine.

In addition to its role in inflammation and immune response, CXCL6 has been implicated in several disease processes, including cancer, atherosclerosis, and rheumatoid arthritis. Elevated levels of CXCL6 have been found in the tumor microenvironment, where it may promote tumor growth and metastasis by recruiting immune cells that support tumor progression.

Cell movement, also known as cell motility, refers to the ability of cells to move independently and change their location within tissue or inside the body. This process is essential for various biological functions, including embryonic development, wound healing, immune responses, and cancer metastasis.

There are several types of cell movement, including:

1. **Crawling or mesenchymal migration:** Cells move by extending and retracting protrusions called pseudopodia or filopodia, which contain actin filaments. This type of movement is common in fibroblasts, immune cells, and cancer cells during tissue invasion and metastasis.
2. **Amoeboid migration:** Cells move by changing their shape and squeezing through tight spaces without forming protrusions. This type of movement is often observed in white blood cells (leukocytes) as they migrate through the body to fight infections.
3. **Pseudopodial extension:** Cells extend pseudopodia, which are temporary cytoplasmic projections containing actin filaments. These protrusions help the cell explore its environment and move forward.
4. **Bacterial flagellar motion:** Bacteria use a whip-like structure called a flagellum to propel themselves through their environment. The rotation of the flagellum is driven by a molecular motor in the bacterial cell membrane.
5. **Ciliary and ependymal movement:** Ciliated cells, such as those lining the respiratory tract and fallopian tubes, have hair-like structures called cilia that beat in coordinated waves to move fluids or mucus across the cell surface.

Cell movement is regulated by a complex interplay of signaling pathways, cytoskeletal rearrangements, and adhesion molecules, which enable cells to respond to environmental cues and navigate through tissues.

Chemokine (C-X-C motif) ligand 1 (CXCL1), also known as growth-regulated oncogene-alpha (GRO-α), is a small signaling protein belonging to the chemokine family. Chemokines are a group of cytokines, or cell signaling molecules, that play important roles in immune responses and inflammation by recruiting immune cells to sites of infection or tissue injury.

CXCL1 specifically binds to and activates the CXCR2 receptor, which is found on various types of immune cells, such as neutrophils, monocytes, and lymphocytes. The activation of the CXCR2 receptor by CXCL1 leads to a series of intracellular signaling events that result in the directed migration of these immune cells towards the site of chemokine production.

CXCL1 is involved in various physiological and pathological processes, including wound healing, angiogenesis, and tumor growth and metastasis. It has been implicated in several inflammatory diseases, such as rheumatoid arthritis, psoriasis, and atherosclerosis, as well as in cancer progression and metastasis.

Chemotaxis, Leukocyte is the movement of leukocytes (white blood cells) towards a higher concentration of a particular chemical substance, known as a chemotactic factor. This process plays a crucial role in the immune system's response to infection and injury.

When there is an infection or tissue damage, certain cells release chemotactic factors, which are small molecules or proteins that can attract leukocytes to the site of inflammation. Leukocytes have receptors on their surface that can detect these chemotactic factors and move towards them through a process called chemotaxis.

Once they reach the site of inflammation, leukocytes can help eliminate pathogens or damaged cells by phagocytosis (engulfing and destroying) or releasing toxic substances that kill the invading microorganisms. Chemotaxis is an essential part of the immune system's defense mechanisms and helps to maintain tissue homeostasis and prevent the spread of infection.

Chemokine (C-X-C motif) ligand 13 (CXCL13), also known as B cell-attracting chemokine 1 (BCA-1) or B lymphocyte chemoattractant (BLC), is a small signaling protein belonging to the CXC chemokine family. Chemokines are a group of chemotactic cytokines that play crucial roles in immunological and inflammatory processes, mainly by recruiting and activating various leukocytes.

CXCL13 is primarily produced by stromal cells, including follicular dendritic cells (FDCs) within secondary lymphoid organs such as lymph nodes, spleen, and Peyer's patches. This chemokine specifically binds to the C-X-C chemokine receptor type 5 (CXCR5), which is expressed on various immune cells, most notably B cells, follicular helper T cells (Tfh), and some dendritic cell subsets.

The primary function of CXCL13 is to orchestrate the migration and positioning of immune cells, particularly B cells, within secondary lymphoid organs during an immune response. By attracting CXCR5-expressing B cells and Tfh cells, CXCL13 plays a critical role in the formation and maintenance of germinal centers (GCs), which are specialized microanatomical structures where affinity maturation and class switch recombination of B cells occur.

Abnormal levels or functions of CXCL13 have been implicated in several pathological conditions, including autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus (SLE), certain types of cancer, and neurological disorders like multiple sclerosis (MS) and Alzheimer's disease.

Chemokines are a family of small cytokines, or signaling proteins, that are secreted by cells and play an important role in the immune system. They are chemotactic, meaning they can attract and guide the movement of various immune cells to specific locations within the body. Chemokines do this by binding to G protein-coupled receptors on the surface of target cells, initiating a signaling cascade that leads to cell migration.

There are four main subfamilies of chemokines, classified based on the arrangement of conserved cysteine residues near the amino terminus: CXC, CC, C, and CX3C. Different chemokines have specific roles in inflammation, immune surveillance, hematopoiesis, and development. Dysregulation of chemokine function has been implicated in various diseases, including autoimmune disorders, infections, and cancer.

In summary, Chemokines are a group of signaling proteins that play a crucial role in the immune system by directing the movement of immune cells to specific locations within the body, thus helping to coordinate the immune response.

Interleukin-8 (IL-8) is a type of cytokine, which is a small signaling protein involved in immune response and inflammation. IL-8 is also known as neutrophil chemotactic factor or NCF because it attracts neutrophils, a type of white blood cell, to the site of infection or injury.

IL-8 is produced by various cells including macrophages, epithelial cells, and endothelial cells in response to bacterial or inflammatory stimuli. It acts by binding to specific receptors called CXCR1 and CXCR2 on the surface of neutrophils, which triggers a series of intracellular signaling events leading to neutrophil activation, migration, and degranulation.

IL-8 plays an important role in the recruitment of neutrophils to the site of infection or tissue damage, where they can phagocytose and destroy invading microorganisms. However, excessive or prolonged production of IL-8 has been implicated in various inflammatory diseases such as chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, and cancer.

Flow cytometry is a medical and research technique used to measure physical and chemical characteristics of cells or particles, one cell at a time, as they flow in a fluid stream through a beam of light. The properties measured include:

* Cell size (light scatter)
* Cell internal complexity (granularity, also light scatter)
* Presence or absence of specific proteins or other molecules on the cell surface or inside the cell (using fluorescent antibodies or other fluorescent probes)

The technique is widely used in cell counting, cell sorting, protein engineering, biomarker discovery and monitoring disease progression, particularly in hematology, immunology, and cancer research.

CCR7 (C-C chemokine receptor type 7) is a type of protein found on the surface of certain immune cells, including T cells and dendritic cells. It is a type of G protein-coupled receptor that binds to specific chemokines, which are small signaling proteins that help regulate the migration and activation of immune cells during an immune response.

CCR7 recognizes and binds to two main chemokines, CCL19 and CCL21, which are produced by specialized cells in lymphoid organs such as lymph nodes and the spleen. When CCR7 on an immune cell binds to one of these chemokines, it triggers a series of intracellular signaling events that cause the cell to migrate towards the source of the chemokine.

This process is important for the proper functioning of the immune system, as it helps to coordinate the movement of immune cells between different tissues and organs during an immune response. For example, dendritic cells in the peripheral tissues can use CCR7 to migrate to the draining lymph nodes, where they can present antigens to T cells and help stimulate an adaptive immune response. Similarly, activated T cells can use CCR7 to migrate to the site of an infection or inflammation, where they can carry out their effector functions.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

CCR4 (C-C chemokine receptor type 4) is a type of protein found on the surface of certain immune cells, including T lymphocytes and regulatory T cells. It is a type of G protein-coupled receptor that binds to specific chemokines, which are small signaling proteins involved in inflammation and immunity.

CCR4 binds to chemokines such as CCL17 (thymus and activation-regulated chemokine) and CCL22 (macrophage-derived chemokine), which are produced by various cell types, including dendritic cells, macrophages, and endothelial cells. The binding of these chemokines to CCR4 triggers a series of intracellular signaling events that regulate the migration and activation of immune cells.

CCR4 has been implicated in several physiological and pathological processes, including the development of Th2-mediated immune responses, allergic inflammation, and cancer. In particular, CCR4 has been identified as a potential therapeutic target for the treatment of certain types of cancer, such as adult T-cell leukemia/lymphoma and cutaneous T-cell lymphoma, due to its role in promoting the recruitment and activation of tumor-associated immune cells.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

C57BL/6 (C57 Black 6) is an inbred strain of laboratory mouse that is widely used in biomedical research. The term "inbred" refers to a strain of animals where matings have been carried out between siblings or other closely related individuals for many generations, resulting in a population that is highly homozygous at most genetic loci.

The C57BL/6 strain was established in 1920 by crossing a female mouse from the dilute brown (DBA) strain with a male mouse from the black strain. The resulting offspring were then interbred for many generations to create the inbred C57BL/6 strain.

C57BL/6 mice are known for their robust health, longevity, and ease of handling, making them a popular choice for researchers. They have been used in a wide range of biomedical research areas, including studies of cancer, immunology, neuroscience, cardiovascular disease, and metabolism.

One of the most notable features of the C57BL/6 strain is its sensitivity to certain genetic modifications, such as the introduction of mutations that lead to obesity or impaired glucose tolerance. This has made it a valuable tool for studying the genetic basis of complex diseases and traits.

Overall, the C57BL/6 inbred mouse strain is an important model organism in biomedical research, providing a valuable resource for understanding the genetic and molecular mechanisms underlying human health and disease.

A ligand, in the context of biochemistry and medicine, is a molecule that binds to a specific site on a protein or a larger biomolecule, such as an enzyme or a receptor. This binding interaction can modify the function or activity of the target protein, either activating it or inhibiting it. Ligands can be small molecules, like hormones or neurotransmitters, or larger structures, like antibodies. The study of ligand-protein interactions is crucial for understanding cellular processes and developing drugs, as many therapeutic compounds function by binding to specific targets within the body.

Warts are small, rough growths on the skin or mucous membranes caused by one of several types of human papillomavirus (HPV). They can appear anywhere on the body but most often occur on the hands, fingers, and feet. Warts are benign, non-cancerous growths, but they can be unsightly, uncomfortable, or painful, depending on their location and size.

Warts are caused by HPV infecting the top layer of skin, usually through a small cut or scratch. The virus triggers an overproduction of keratin, a protein in the skin, leading to the formation of a hard, rough growth. Warts can vary in appearance depending on their location and type, but they are generally round or irregularly shaped, with a rough surface that may be flat or slightly raised. They may also contain small black dots, which are actually tiny blood vessels that have clotted.

Warts are contagious and can spread from person to person through direct skin-to-skin contact or by sharing personal items such as towels or razors. They can also be spread by touching a wart and then touching another part of the body. Warts may take several months to develop after exposure to HPV, so it may not always be clear when or how they were contracted.

There are several types of warts, including common warts, plantar warts (which occur on the soles of the feet), flat warts (which are smaller and smoother than other types of warts), and genital warts (which are sexually transmitted). While most warts are harmless and will eventually go away on their own, some may require medical treatment if they are causing discomfort or are unsightly. Treatment options for warts include topical medications, cryotherapy (freezing the wart with liquid nitrogen), and surgical removal.

A cell line that is derived from tumor cells and has been adapted to grow in culture. These cell lines are often used in research to study the characteristics of cancer cells, including their growth patterns, genetic changes, and responses to various treatments. They can be established from many different types of tumors, such as carcinomas, sarcomas, and leukemias. Once established, these cell lines can be grown and maintained indefinitely in the laboratory, allowing researchers to conduct experiments and studies that would not be feasible using primary tumor cells. It is important to note that tumor cell lines may not always accurately represent the behavior of the original tumor, as they can undergo genetic changes during their time in culture.

A "knockout" mouse is a genetically engineered mouse in which one or more genes have been deleted or "knocked out" using molecular biology techniques. This allows researchers to study the function of specific genes and their role in various biological processes, as well as potential associations with human diseases. The mice are generated by introducing targeted DNA modifications into embryonic stem cells, which are then used to create a live animal. Knockout mice have been widely used in biomedical research to investigate gene function, disease mechanisms, and potential therapeutic targets.

HIV receptors are specific molecules found on the surface of certain human cells that the Human Immunodeficiency Virus (HIV) uses to enter and infect those cells. The two primary HIV receptors are CD4 and CCR5 or CXCR4 co-receptors.

1. CD4 Receptor: This is a glycoprotein found on the surface of helper T cells, macrophages, and dendritic cells. HIV first binds to the CD4 receptor via its envelope protein gp120. However, this binding alone is not sufficient for virus entry. The interaction between gp120 and CD4 triggers conformational changes in the viral envelope that expose the binding site for a co-receptor.

2. CCR5 or CXCR4 Co-receptors: These are chemokine receptors also found on the surface of certain cells, including helper T cells and macrophages. After HIV binds to the CD4 receptor, it interacts with either the CCR5 or CXCR4 co-receptor, which facilitates the fusion of the viral and cell membranes and the release of the viral genetic material into the host cell.

The specificity of HIV for these receptors plays a crucial role in its pathogenesis, as it determines which cells are susceptible to infection. Additionally, variations in the genes encoding these receptors can influence an individual's susceptibility to HIV infection and the rate of disease progression.

Cytokine receptors are specialized protein molecules found on the surface of cells that selectively bind to specific cytokines. Cytokines are signaling molecules used for communication between cells, and they play crucial roles in regulating immune responses, inflammation, hematopoiesis, and cell survival.

Cytokine receptors have specific binding sites that recognize and interact with the corresponding cytokines. This interaction triggers a series of intracellular signaling events that ultimately lead to changes in gene expression and various cellular responses. Cytokine receptors can be found on many different types of cells, including immune cells, endothelial cells, and structural cells like fibroblasts.

Cytokine receptors are typically composed of multiple subunits, which may include both extracellular and intracellular domains. The extracellular domain is responsible for cytokine binding, while the intracellular domain is involved in signal transduction. Cytokine receptors can be classified into several families based on their structural features and signaling mechanisms, such as the hematopoietic cytokine receptor family, the interferon receptor family, the tumor necrosis factor receptor family, and the interleukin-1 receptor family.

Dysregulation of cytokine receptors and their signaling pathways has been implicated in various diseases, including autoimmune disorders, chronic inflammation, and cancer. Therefore, understanding the biology of cytokine receptors is essential for developing targeted therapies to treat these conditions.

Immunohistochemistry (IHC) is a technique used in pathology and laboratory medicine to identify specific proteins or antigens in tissue sections. It combines the principles of immunology and histology to detect the presence and location of these target molecules within cells and tissues. This technique utilizes antibodies that are specific to the protein or antigen of interest, which are then tagged with a detection system such as a chromogen or fluorophore. The stained tissue sections can be examined under a microscope, allowing for the visualization and analysis of the distribution and expression patterns of the target molecule in the context of the tissue architecture. Immunohistochemistry is widely used in diagnostic pathology to help identify various diseases, including cancer, infectious diseases, and immune-mediated disorders.

Up-regulation is a term used in molecular biology and medicine to describe an increase in the expression or activity of a gene, protein, or receptor in response to a stimulus. This can occur through various mechanisms such as increased transcription, translation, or reduced degradation of the molecule. Up-regulation can have important functional consequences, for example, enhancing the sensitivity or response of a cell to a hormone, neurotransmitter, or drug. It is a normal physiological process that can also be induced by disease or pharmacological interventions.

Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is a laboratory technique used in molecular biology to amplify and detect specific DNA sequences. This technique is particularly useful for the detection and quantification of RNA viruses, as well as for the analysis of gene expression.

The process involves two main steps: reverse transcription and polymerase chain reaction (PCR). In the first step, reverse transcriptase enzyme is used to convert RNA into complementary DNA (cDNA) by reading the template provided by the RNA molecule. This cDNA then serves as a template for the PCR amplification step.

In the second step, the PCR reaction uses two primers that flank the target DNA sequence and a thermostable polymerase enzyme to repeatedly copy the targeted cDNA sequence. The reaction mixture is heated and cooled in cycles, allowing the primers to anneal to the template, and the polymerase to extend the new strand. This results in exponential amplification of the target DNA sequence, making it possible to detect even small amounts of RNA or cDNA.

RT-PCR is a sensitive and specific technique that has many applications in medical research and diagnostics, including the detection of viruses such as HIV, hepatitis C virus, and SARS-CoV-2 (the virus that causes COVID-19). It can also be used to study gene expression, identify genetic mutations, and diagnose genetic disorders.

CCR5 (C-C chemokine receptor type 5) is a type of protein found on the surface of certain white blood cells, including T-cells, macrophages, and dendritic cells. It belongs to the family of G protein-coupled receptors, which are involved in various cellular responses.

CCR5 acts as a co-receptor for HIV (Human Immunodeficiency Virus) entry into host cells, along with CD4. The virus binds to both CCR5 and CD4, leading to fusion of the viral and cell membranes and subsequent infection of the cell.

Individuals who have a genetic mutation that prevents CCR5 from functioning are resistant to HIV infection, highlighting its importance in the viral life cycle. Additionally, CCR5 antagonists have been developed as potential therapeutic agents for the treatment of HIV infection.

T-lymphocytes, also known as T-cells, are a type of white blood cell that plays a key role in the adaptive immune system's response to infection. They are produced in the bone marrow and mature in the thymus gland. There are several different types of T-cells, including CD4+ helper T-cells, CD8+ cytotoxic T-cells, and regulatory T-cells (Tregs).

CD4+ helper T-cells assist in activating other immune cells, such as B-lymphocytes and macrophages. They also produce cytokines, which are signaling molecules that help coordinate the immune response. CD8+ cytotoxic T-cells directly kill infected cells by releasing toxic substances. Regulatory T-cells help maintain immune tolerance and prevent autoimmune diseases by suppressing the activity of other immune cells.

T-lymphocytes are important in the immune response to viral infections, cancer, and other diseases. Dysfunction or depletion of T-cells can lead to immunodeficiency and increased susceptibility to infections. On the other hand, an overactive T-cell response can contribute to autoimmune diseases and chronic inflammation.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

Neutrophils are a type of white blood cell that are part of the immune system's response to infection. They are produced in the bone marrow and released into the bloodstream where they circulate and are able to move quickly to sites of infection or inflammation in the body. Neutrophils are capable of engulfing and destroying bacteria, viruses, and other foreign substances through a process called phagocytosis. They are also involved in the release of inflammatory mediators, which can contribute to tissue damage in some cases. Neutrophils are characterized by the presence of granules in their cytoplasm, which contain enzymes and other proteins that help them carry out their immune functions.

Chemokine (C-X-C motif) ligand 5 (CXCL5), also known as epithelial neutrophil-activating peptide 78 (ENA-78) or liver-activated peptide (LAP), is a small signaling protein belonging to the CXC chemokine family. Chemokines are a group of cytokines, or cell signaling molecules, that play important roles in immune responses and inflammation by recruiting various immune cells to sites of infection or injury through specific receptor-mediated interactions.

CXCL5 is primarily produced by epithelial cells, macrophages, and neutrophils in response to bacterial infections, tissue damage, or proinflammatory cytokines. This chemokine exerts its functions by binding to its receptor CXCR2, which is expressed on the surface of various immune cells, including neutrophils, monocytes, and lymphocytes. The primary role of CXCL5 is to attract neutrophils to the site of inflammation or infection, where they can help eliminate pathogens and promote tissue repair.

Apart from its involvement in immune responses and inflammation, CXCL5 has been implicated in several physiological and pathological processes, such as embryonic development, wound healing, cancer progression, and metastasis. Dysregulation of CXCL5 signaling has been associated with various diseases, including chronic inflammatory disorders, autoimmune diseases, and cancer.

Cell proliferation is the process by which cells increase in number, typically through the process of cell division. In the context of biology and medicine, it refers to the reproduction of cells that makes up living tissue, allowing growth, maintenance, and repair. It involves several stages including the transition from a phase of quiescence (G0 phase) to an active phase (G1 phase), DNA replication in the S phase, and mitosis or M phase, where the cell divides into two daughter cells.

Abnormal or uncontrolled cell proliferation is a characteristic feature of many diseases, including cancer, where deregulated cell cycle control leads to excessive and unregulated growth of cells, forming tumors that can invade surrounding tissues and metastasize to distant sites in the body.

HIV-1 (Human Immunodeficiency Virus type 1) is a species of the retrovirus genus that causes acquired immunodeficiency syndrome (AIDS). It is primarily transmitted through sexual contact, exposure to infected blood or blood products, and from mother to child during pregnancy, childbirth, or breastfeeding. HIV-1 infects vital cells in the human immune system, such as CD4+ T cells, macrophages, and dendritic cells, leading to a decline in their numbers and weakening of the immune response over time. This results in the individual becoming susceptible to various opportunistic infections and cancers that ultimately cause death if left untreated. HIV-1 is the most prevalent form of HIV worldwide and has been identified as the causative agent of the global AIDS pandemic.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

Stromal cells, also known as stromal/stroma cells, are a type of cell found in various tissues and organs throughout the body. They are often referred to as the "connective tissue" or "supporting framework" of an organ because they play a crucial role in maintaining the structure and function of the tissue. Stromal cells include fibroblasts, adipocytes (fat cells), and various types of progenitor/stem cells. They produce and maintain the extracellular matrix, which is the non-cellular component of tissues that provides structural support and biochemical cues for other cells. Stromal cells also interact with immune cells and participate in the regulation of the immune response. In some contexts, "stromal cells" can also refer to cells found in the microenvironment of tumors, which can influence cancer growth and progression.

Scavenger receptors are a class of cell surface receptors that play a crucial role in the recognition and clearance of various biomolecules, including modified self-molecules, pathogens, and apoptotic cells. These receptors are expressed mainly by phagocytic cells such as macrophages and dendritic cells, but they can also be found on other cell types, including endothelial cells and smooth muscle cells.

Scavenger receptors have broad specificity and can bind to a wide range of ligands, including oxidized low-density lipoprotein (oxLDL), polyanionic molecules, advanced glycation end products (AGEs), and pathogen-associated molecular patterns (PAMPs). The binding of ligands to scavenger receptors triggers various cellular responses, such as phagocytosis, endocytosis, signaling cascades, and the production of cytokines and chemokines.

Scavenger receptors are classified into several families based on their structural features and ligand specificity, including:

1. Class A (SR-A): This family includes SR-AI, SR-AII, and MARCO, which bind to oxLDL, bacteria, and apoptotic cells.
2. Class B (SR-B): This family includes SR-BI, CD36, and LIMPII, which bind to lipoproteins, phospholipids, and pathogens.
3. Class C (SR-C): This family includes DEC-205, MRC1, and LOX-1, which bind to various ligands, including apoptotic cells, bacteria, and oxLDL.
4. Class D (SR-D): This family includes SCARF1, which binds to PAMPs and damage-associated molecular patterns (DAMPs).
5. Class E (SR-E): This family includes CXCL16, which binds to chemokine CXCR6 and phosphatidylserine.

Scavenger receptors play a critical role in maintaining tissue homeostasis by removing damaged or altered molecules and cells, modulating immune responses, and regulating lipid metabolism. Dysregulation of scavenger receptor function has been implicated in various pathological conditions, including atherosclerosis, inflammation, infection, and cancer.

Feline Immunodeficiency Virus (FIV) is a lentivirus that primarily affects felines, including domestic cats and wild cats. It is the feline equivalent of Human Immunodeficiency Virus (HIV). The virus attacks the immune system, specifically the CD4+ T-cells, leading to a decline in the immune function over time.

This makes the infected cat more susceptible to various secondary infections and diseases. It is usually transmitted through bite wounds from infected cats during fighting or mating. Mother to offspring transmission can also occur, either in utero, during birth, or through nursing.

There is no cure for FIV, but antiretroviral therapy can help manage the disease and improve the quality of life for infected cats. It's important to note that while FIV-positive cats can live normal lives for many years, they should be kept indoors to prevent transmission to other cats and to protect them from opportunistic infections.

HIV Envelope Protein gp120 is a glycoprotein that is a major component of the outer envelope of the Human Immunodeficiency Virus (HIV). It plays a crucial role in the viral infection process. The "gp" stands for glycoprotein.

The gp120 protein is responsible for binding to CD4 receptors on the surface of human immune cells, particularly T-helper cells or CD4+ cells. This binding initiates the fusion process that allows the virus to enter and infect the cell.

After attachment, a series of conformational changes occur in the gp120 and another envelope protein, gp41, leading to the formation of a bridge between the viral and cell membranes, which ultimately results in the virus entering the host cell.

The gp120 protein is also one of the primary targets for HIV vaccine design due to its critical role in the infection process and its surface location, making it accessible to the immune system. However, its high variability and ability to evade the immune response have posed significant challenges in developing an effective HIV vaccine.

The lateral line system is a sensory organ found in aquatic animals, such as fish and some aquatic amphibians. It is a series of fluid-filled canals and sensory cells that run along the sides of the body, head, and fins. These sensory cells are called neuromasts and contain hair cells that respond to vibrations and water movements. The lateral line system helps these animals detect movement, pressure changes, and vibrations in their aquatic environment, which aids in schooling behavior, prey detection, and avoiding predators.

SCID mice is an acronym for Severe Combined Immunodeficiency mice. These are genetically modified mice that lack a functional immune system due to the mutation or knockout of several key genes required for immunity. This makes them ideal for studying the human immune system, infectious diseases, and cancer, as well as testing new therapies and treatments in a controlled environment without the risk of interference from the mouse's own immune system. SCID mice are often used in xenotransplantation studies, where human cells or tissues are transplanted into the mouse to study their behavior and interactions with the human immune system.

Arrestins are a family of proteins that play a crucial role in regulating G protein-coupled receptor (GPCR) signaling. There are four main types of arrestins: visual arrestin (also known as arr1 or S-arrestin), β-arrestin1 (also known as arr2 or Kon/Vec), β-arrestin2 (also known as arr3 or hTHT), and arrestin-domain containing protein 1 (ARRDC1).

Arrestins bind to the intracellular domains of activated GPCRs, which leads to several outcomes:

1. They prevent further activation of G proteins by the receptor, effectively "arresting" the signal transduction process.
2. They promote the internalization (endocytosis) of the receptor from the cell membrane into endosomes, where it can be either degraded or recycled back to the cell surface.
3. They act as scaffolds for various signaling complexes and mediate interactions between GPCRs and other intracellular signaling proteins, leading to the activation of different signaling pathways.

Overall, arrestins play a critical role in fine-tuning GPCR signaling, ensuring appropriate cellular responses to hormones, neurotransmitters, and other extracellular signals.

Neoplasm invasiveness is a term used in pathology and oncology to describe the aggressive behavior of cancer cells as they invade surrounding tissues and organs. This process involves the loss of cell-to-cell adhesion, increased motility and migration, and the ability of cancer cells to degrade the extracellular matrix (ECM) through the production of enzymes such as matrix metalloproteinases (MMPs).

Invasive neoplasms are cancers that have spread beyond the original site where they first developed and have infiltrated adjacent tissues or structures. This is in contrast to non-invasive or in situ neoplasms, which are confined to the epithelial layer where they originated and have not yet invaded the underlying basement membrane.

The invasiveness of a neoplasm is an important prognostic factor in cancer diagnosis and treatment, as it can indicate the likelihood of metastasis and the potential effectiveness of various therapies. In general, more invasive cancers are associated with worse outcomes and require more aggressive treatment approaches.

Chemokine (C-X-C motif) ligand 2, also known as CXCL2, is a small signaling protein that belongs to the chemokine family. Chemokines are a group of cytokines, or cell signaling molecules, that play crucial roles in immune responses and inflammation. They mediate their effects by interacting with specific receptors on the surface of target cells, guiding the migration of various immune cells to sites of infection, injury, or inflammation.

CXCL2 is primarily produced by activated monocytes, macrophages, and neutrophils, as well as endothelial cells, fibroblasts, and certain types of tumor cells. Its primary function is to attract and activate neutrophils, which are key effector cells in the early stages of inflammation and host defense against invading pathogens. CXCL2 exerts its effects by binding to its specific receptor, CXCR2, which is expressed on the surface of neutrophils and other immune cells.

In addition to its role in inflammation and immunity, CXCL2 has been implicated in various pathological conditions, including cancer, atherosclerosis, and autoimmune diseases. Its expression can be regulated by several factors, such as pro-inflammatory cytokines, bacterial products, and growth factors. Understanding the role of CXCL2 in health and disease may provide insights into the development of novel therapeutic strategies for treating inflammation-associated disorders.

Chemotactic factors are substances that attract or repel cells, particularly immune cells, by stimulating directional movement in response to a chemical gradient. These factors play a crucial role in the body's immune response and inflammation process. They include:

1. Chemokines: A family of small signaling proteins that direct the migration of immune cells to sites of infection or tissue damage.
2. Cytokines: A broad category of signaling molecules that mediate and regulate immunity, inflammation, and hematopoiesis. Some cytokines can also act as chemotactic factors.
3. Complement components: Cleavage products of the complement system can attract immune cells to the site of infection or tissue injury.
4. Growth factors: Certain growth factors, like colony-stimulating factors (CSFs), can stimulate the migration and proliferation of specific cell types.
5. Lipid mediators: Products derived from arachidonic acid metabolism, such as leukotrienes and prostaglandins, can also act as chemotactic factors.
6. Formyl peptides: Bacterial-derived formylated peptides can attract and activate neutrophils during an infection.
7. Extracellular matrix (ECM) components: Fragments of ECM proteins, like collagen and fibronectin, can serve as chemotactic factors for immune cells.

These factors help orchestrate the immune response by guiding the movement of immune cells to specific locations in the body where they are needed.

Intercellular signaling peptides and proteins are molecules that mediate communication and interaction between different cells in living organisms. They play crucial roles in various biological processes, including cell growth, differentiation, migration, and apoptosis (programmed cell death). These signals can be released into the extracellular space, where they bind to specific receptors on the target cell's surface, triggering intracellular signaling cascades that ultimately lead to a response.

Peptides are short chains of amino acids, while proteins are larger molecules made up of one or more polypeptide chains. Both can function as intercellular signaling molecules by acting as ligands for cell surface receptors or by being cleaved from larger precursor proteins and released into the extracellular space. Examples of intercellular signaling peptides and proteins include growth factors, cytokines, chemokines, hormones, neurotransmitters, and their respective receptors.

These molecules contribute to maintaining homeostasis within an organism by coordinating cellular activities across tissues and organs. Dysregulation of intercellular signaling pathways has been implicated in various diseases, such as cancer, autoimmune disorders, and neurodegenerative conditions. Therefore, understanding the mechanisms underlying intercellular signaling is essential for developing targeted therapies to treat these disorders.

Neutrophil infiltration is a pathological process characterized by the accumulation of neutrophils, a type of white blood cell, in tissue. It is a common feature of inflammation and occurs in response to infection, injury, or other stimuli that trigger an immune response. Neutrophils are attracted to the site of tissue damage by chemical signals called chemokines, which are released by damaged cells and activated immune cells. Once they reach the site of inflammation, neutrophils help to clear away damaged tissue and microorganisms through a process called phagocytosis. However, excessive or prolonged neutrophil infiltration can also contribute to tissue damage and may be associated with various disease states, including cancer, autoimmune disorders, and ischemia-reperfusion injury.

Chemokine (C-C motif) ligand 21 (CCL21), also known as secondary lymphoid tissue chemokine (SLC) or exodus-2, is a type of chemokine that belongs to the CC subfamily. Chemokines are small signaling proteins that play crucial roles in regulating immune responses and inflammation by recruiting various leukocytes to sites of infection or injury through specific receptor binding.

CCL21 is primarily expressed in high endothelial venules (HEVs) within lymphoid tissues, such as lymph nodes, spleen, and Peyer's patches. It functions as a chemoattractant for immune cells like dendritic cells, T cells, and B cells, guiding them to enter the HEVs and migrate into the lymphoid organs. This process is essential for initiating adaptive immune responses against pathogens or antigens.

CCL21 exerts its effects by binding to chemokine receptors CCR7 and atypical chemokine receptor ACKR3 (also known as CXCR7). The interaction between CCL21 and these receptors triggers intracellular signaling cascades, leading to cell migration and activation. Dysregulation of CCL21 expression or function has been implicated in various pathological conditions, including autoimmune diseases, cancer, and inflammatory disorders.

Jurkat cells are a type of human immortalized T lymphocyte (a type of white blood cell) cell line that is commonly used in scientific research. They were originally isolated from the peripheral blood of a patient with acute T-cell leukemia. Jurkat cells are widely used as a model system to study T-cell activation, signal transduction, and apoptosis (programmed cell death). They are also used in the study of HIV infection and replication, as they can be infected with the virus and used to investigate viral replication and host cell responses.

BALB/c is an inbred strain of laboratory mouse that is widely used in biomedical research. The strain was developed at the Institute of Cancer Research in London by Henry Baldwin and his colleagues in the 1920s, and it has since become one of the most commonly used inbred strains in the world.

BALB/c mice are characterized by their black coat color, which is determined by a recessive allele at the tyrosinase locus. They are also known for their docile and friendly temperament, making them easy to handle and work with in the laboratory.

One of the key features of BALB/c mice that makes them useful for research is their susceptibility to certain types of tumors and immune responses. For example, they are highly susceptible to developing mammary tumors, which can be induced by chemical carcinogens or viral infection. They also have a strong Th2-biased immune response, which makes them useful models for studying allergic diseases and asthma.

BALB/c mice are also commonly used in studies of genetics, neuroscience, behavior, and infectious diseases. Because they are an inbred strain, they have a uniform genetic background, which makes it easier to control for genetic factors in experiments. Additionally, because they have been bred in the laboratory for many generations, they are highly standardized and reproducible, making them ideal subjects for scientific research.

Receptor cross-talk, also known as receptor crosstalk or cross-communication, refers to the phenomenon where two or more receptors in a cell interact with each other and modulate their signals in a coordinated manner. This interaction can occur at various levels, such as sharing downstream signaling pathways, physically interacting with each other, or influencing each other's expression or activity.

In the context of G protein-coupled receptors (GPCRs), which are a large family of membrane receptors that play crucial roles in various physiological processes, cross-talk can occur between different GPCRs or between GPCRs and other types of receptors. For example, one GPCR may activate a signaling pathway that inhibits the activity of another GPCR, leading to complex regulatory mechanisms that allow cells to fine-tune their responses to various stimuli.

Receptor cross-talk can have important implications for drug development and therapy, as it can affect the efficacy and safety of drugs that target specific receptors. Understanding the mechanisms of receptor cross-talk can help researchers design more effective and targeted therapies for a wide range of diseases.

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

Bone marrow cells are the types of cells found within the bone marrow, which is the spongy tissue inside certain bones in the body. The main function of bone marrow is to produce blood cells. There are two types of bone marrow: red and yellow. Red bone marrow is where most blood cell production takes place, while yellow bone marrow serves as a fat storage site.

The three main types of bone marrow cells are:

1. Hematopoietic stem cells (HSCs): These are immature cells that can differentiate into any type of blood cell, including red blood cells, white blood cells, and platelets. They have the ability to self-renew, meaning they can divide and create more hematopoietic stem cells.
2. Red blood cell progenitors: These are immature cells that will develop into mature red blood cells, also known as erythrocytes. Red blood cells carry oxygen from the lungs to the body's tissues and carbon dioxide back to the lungs.
3. Myeloid and lymphoid white blood cell progenitors: These are immature cells that will develop into various types of white blood cells, which play a crucial role in the body's immune system by fighting infections and diseases. Myeloid progenitors give rise to granulocytes (neutrophils, eosinophils, and basophils), monocytes, and megakaryocytes (which eventually become platelets). Lymphoid progenitors differentiate into B cells, T cells, and natural killer (NK) cells.

Bone marrow cells are essential for maintaining a healthy blood cell count and immune system function. Abnormalities in bone marrow cells can lead to various medical conditions, such as anemia, leukopenia, leukocytosis, thrombocytopenia, or thrombocytosis, depending on the specific type of blood cell affected. Additionally, bone marrow cells are often used in transplantation procedures to treat patients with certain types of cancer, such as leukemia and lymphoma, or other hematologic disorders.

CD4 antigens, also known as CD4 proteins or CD4 molecules, are a type of cell surface receptor found on certain immune cells, including T-helper cells and monocytes. They play a critical role in the immune response by binding to class II major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells and helping to activate T-cells. CD4 antigens are also the primary target of the human immunodeficiency virus (HIV), which causes AIDS, leading to the destruction of CD4-positive T-cells and a weakened immune system.

Down-regulation is a process that occurs in response to various stimuli, where the number or sensitivity of cell surface receptors or the expression of specific genes is decreased. This process helps maintain homeostasis within cells and tissues by reducing the ability of cells to respond to certain signals or molecules.

In the context of cell surface receptors, down-regulation can occur through several mechanisms:

1. Receptor internalization: After binding to their ligands, receptors can be internalized into the cell through endocytosis. Once inside the cell, these receptors may be degraded or recycled back to the cell surface in smaller numbers.
2. Reduced receptor synthesis: Down-regulation can also occur at the transcriptional level, where the expression of genes encoding for specific receptors is decreased, leading to fewer receptors being produced.
3. Receptor desensitization: Prolonged exposure to a ligand can lead to a decrease in receptor sensitivity or affinity, making it more difficult for the cell to respond to the signal.

In the context of gene expression, down-regulation refers to the decreased transcription and/or stability of specific mRNAs, leading to reduced protein levels. This process can be induced by various factors, including microRNA (miRNA)-mediated regulation, histone modification, or DNA methylation.

Down-regulation is an essential mechanism in many physiological processes and can also contribute to the development of several diseases, such as cancer and neurodegenerative disorders.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

CD4-positive T-lymphocytes, also known as CD4+ T cells or helper T cells, are a type of white blood cell that plays a crucial role in the immune response. They express the CD4 receptor on their surface and help coordinate the immune system's response to infectious agents such as viruses and bacteria.

CD4+ T cells recognize and bind to specific antigens presented by antigen-presenting cells, such as dendritic cells or macrophages. Once activated, they can differentiate into various subsets of effector cells, including Th1, Th2, Th17, and Treg cells, each with distinct functions in the immune response.

CD4+ T cells are particularly important in the immune response to HIV (human immunodeficiency virus), which targets and destroys these cells, leading to a weakened immune system and increased susceptibility to opportunistic infections. The number of CD4+ T cells is often used as a marker of disease progression in HIV infection, with lower counts indicating more advanced disease.

Neoplasm metastasis is the spread of cancer cells from the primary site (where the original or primary tumor formed) to other places in the body. This happens when cancer cells break away from the original (primary) tumor and enter the bloodstream or lymphatic system. The cancer cells can then travel to other parts of the body and form new tumors, called secondary tumors or metastases.

Metastasis is a key feature of malignant neoplasms (cancers), and it is one of the main ways that cancer can cause harm in the body. The metastatic tumors may continue to grow and may cause damage to the organs and tissues where they are located. They can also release additional cancer cells into the bloodstream or lymphatic system, leading to further spread of the cancer.

The metastatic tumors are named based on the location where they are found, as well as the type of primary cancer. For example, if a patient has a primary lung cancer that has metastasized to the liver, the metastatic tumor would be called a liver metastasis from lung cancer.

It is important to note that the presence of metastases can significantly affect a person's prognosis and treatment options. In general, metastatic cancer is more difficult to treat than cancer that has not spread beyond its original site. However, there are many factors that can influence a person's prognosis and response to treatment, so it is important for each individual to discuss their specific situation with their healthcare team.

Cell adhesion refers to the binding of cells to extracellular matrices or to other cells, a process that is fundamental to the development, function, and maintenance of multicellular organisms. Cell adhesion is mediated by various cell surface receptors, such as integrins, cadherins, and immunoglobulin-like cell adhesion molecules (Ig-CAMs), which interact with specific ligands in the extracellular environment. These interactions lead to the formation of specialized junctions, such as tight junctions, adherens junctions, and desmosomes, that help to maintain tissue architecture and regulate various cellular processes, including proliferation, differentiation, migration, and survival. Disruptions in cell adhesion can contribute to a variety of diseases, including cancer, inflammation, and degenerative disorders.

Transfection is a term used in molecular biology that refers to the process of deliberately introducing foreign genetic material (DNA, RNA or artificial gene constructs) into cells. This is typically done using chemical or physical methods, such as lipofection or electroporation. Transfection is widely used in research and medical settings for various purposes, including studying gene function, producing proteins, developing gene therapies, and creating genetically modified organisms. It's important to note that transfection is different from transduction, which is the process of introducing genetic material into cells using viruses as vectors.

A zebrafish is a freshwater fish species belonging to the family Cyprinidae and the genus Danio. Its name is derived from its distinctive striped pattern that resembles a zebra's. Zebrafish are often used as model organisms in scientific research, particularly in developmental biology, genetics, and toxicology studies. They have a high fecundity rate, transparent embryos, and a rapid development process, making them an ideal choice for researchers. However, it is important to note that providing a medical definition for zebrafish may not be entirely accurate or relevant since they are primarily used in biological research rather than clinical medicine.

Neoplastic gene expression regulation refers to the processes that control the production of proteins and other molecules from genes in neoplastic cells, or cells that are part of a tumor or cancer. In a normal cell, gene expression is tightly regulated to ensure that the right genes are turned on or off at the right time. However, in cancer cells, this regulation can be disrupted, leading to the overexpression or underexpression of certain genes.

Neoplastic gene expression regulation can be affected by a variety of factors, including genetic mutations, epigenetic changes, and signals from the tumor microenvironment. These changes can lead to the activation of oncogenes (genes that promote cancer growth and development) or the inactivation of tumor suppressor genes (genes that prevent cancer).

Understanding neoplastic gene expression regulation is important for developing new therapies for cancer, as targeting specific genes or pathways involved in this process can help to inhibit cancer growth and progression.

Endothelial cells are the type of cells that line the inner surface of blood vessels, lymphatic vessels, and heart chambers. They play a crucial role in maintaining vascular homeostasis by controlling vasomotor tone, coagulation, platelet activation, and inflammation. Endothelial cells also regulate the transport of molecules between the blood and surrounding tissues, and contribute to the maintenance of the structural integrity of the vasculature. They are flat, elongated cells with a unique morphology that allows them to form a continuous, nonthrombogenic lining inside the vessels. Endothelial cells can be isolated from various tissues and cultured in vitro for research purposes.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Chemokines are a family of small proteins that are involved in immune responses and inflammation. They mediate the chemotaxis (directed migration) of various cells, including leukocytes (white blood cells). Chemokines are classified into four major subfamilies based on the arrangement of conserved cysteine residues near the amino terminus: CXC, CC, C, and CX3C.

CC chemokines, also known as β-chemokines, are characterized by the presence of two adjacent cysteine residues near their N-terminal end. There are 27 known human CC chemokines, including MCP-1 (monocyte chemoattractant protein-1), RANTES (regulated on activation, normal T cell expressed and secreted), and eotaxin.

CC chemokines play important roles in the recruitment of immune cells to sites of infection or injury, as well as in the development and maintenance of immune responses. They bind to specific G protein-coupled receptors (GPCRs) on the surface of target cells, leading to the activation of intracellular signaling pathways that regulate cell migration, proliferation, and survival.

Dysregulation of CC chemokines and their receptors has been implicated in various inflammatory and autoimmune diseases, as well as in cancer. Therefore, targeting CC chemokine-mediated signaling pathways has emerged as a promising therapeutic strategy for the treatment of these conditions.

Virus receptors are specific molecules (commonly proteins) on the surface of host cells that viruses bind to in order to enter and infect those cells. This interaction between the virus and its receptor is a critical step in the infection process. Different types of viruses have different receptor requirements, and identifying these receptors can provide important insights into the biology of the virus and potential targets for antiviral therapies.

Inbred NOD (Nonobese Diabetic) mice are a strain of laboratory mice that are genetically predisposed to develop autoimmune diabetes. This strain was originally developed in Japan and has been widely used as an animal model for studying type 1 diabetes and its complications.

NOD mice typically develop diabetes spontaneously at around 12-14 weeks of age, although the onset and severity of the disease can vary between individual mice. The disease is caused by a breakdown in immune tolerance, leading to an autoimmune attack on the insulin-producing beta cells of the pancreas.

Inbred NOD mice are highly valuable for research purposes because they exhibit many of the same genetic and immunological features as human patients with type 1 diabetes. By studying these mice, researchers can gain insights into the underlying mechanisms of the disease and develop new treatments and therapies.

Interleukin receptors are a type of cell surface receptor that bind and respond to interleukins, which are cytokines involved in the immune response. These receptors play a crucial role in the communication between different cells of the immune system, such as T cells, B cells, and macrophages. Interleukin receptors are typically composed of multiple subunits, some of which may be shared by different interleukin receptors. Upon binding to their respective interleukins, these receptors activate intracellular signaling pathways that regulate various cellular responses, including proliferation, differentiation, and activation of immune cells. Dysregulation of interleukin receptor signaling has been implicated in several diseases, such as autoimmune disorders and cancer.

'Gene expression regulation' refers to the processes that control whether, when, and where a particular gene is expressed, meaning the production of a specific protein or functional RNA encoded by that gene. This complex mechanism can be influenced by various factors such as transcription factors, chromatin remodeling, DNA methylation, non-coding RNAs, and post-transcriptional modifications, among others. Proper regulation of gene expression is crucial for normal cellular function, development, and maintaining homeostasis in living organisms. Dysregulation of gene expression can lead to various diseases, including cancer and genetic disorders.

Cell differentiation is the process by which a less specialized cell, or stem cell, becomes a more specialized cell type with specific functions and structures. This process involves changes in gene expression, which are regulated by various intracellular signaling pathways and transcription factors. Differentiation results in the development of distinct cell types that make up tissues and organs in multicellular organisms. It is a crucial aspect of embryonic development, tissue repair, and maintenance of homeostasis in the body.

Interferon-gamma (IFN-γ) is a soluble cytokine that is primarily produced by the activation of natural killer (NK) cells and T lymphocytes, especially CD4+ Th1 cells and CD8+ cytotoxic T cells. It plays a crucial role in the regulation of the immune response against viral and intracellular bacterial infections, as well as tumor cells. IFN-γ has several functions, including activating macrophages to enhance their microbicidal activity, increasing the presentation of major histocompatibility complex (MHC) class I and II molecules on antigen-presenting cells, stimulating the proliferation and differentiation of T cells and NK cells, and inducing the production of other cytokines and chemokines. Additionally, IFN-γ has direct antiproliferative effects on certain types of tumor cells and can enhance the cytotoxic activity of immune cells against infected or malignant cells.

G-protein-coupled receptors (GPCRs) are a family of membrane receptors that play an essential role in cellular signaling and communication. These receptors possess seven transmembrane domains, forming a structure that spans the lipid bilayer of the cell membrane. They are called "G-protein-coupled" because they interact with heterotrimeric G proteins upon activation, which in turn modulate various downstream signaling pathways.

When an extracellular ligand binds to a GPCR, it causes a conformational change in the receptor's structure, leading to the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP) on the associated G protein's α subunit. This exchange triggers the dissociation of the G protein into its α and βγ subunits, which then interact with various effector proteins to elicit cellular responses.

There are four main families of GPCRs, classified based on their sequence similarities and downstream signaling pathways:

1. Gq-coupled receptors: These receptors activate phospholipase C (PLC), which leads to the production of inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 induces calcium release from intracellular stores, while DAG activates protein kinase C (PKC).
2. Gs-coupled receptors: These receptors activate adenylyl cyclase, which increases the production of cyclic adenosine monophosphate (cAMP) and subsequently activates protein kinase A (PKA).
3. Gi/o-coupled receptors: These receptors inhibit adenylyl cyclase, reducing cAMP levels and modulating PKA activity. Additionally, they can activate ion channels or regulate other signaling pathways through the βγ subunits.
4. G12/13-coupled receptors: These receptors primarily activate RhoGEFs, which in turn activate RhoA and modulate cytoskeletal organization and cellular motility.

GPCRs are involved in various physiological processes, including neurotransmission, hormone signaling, immune response, and sensory perception. Dysregulation of GPCR function has been implicated in numerous diseases, making them attractive targets for drug development.

Phosphorylation is the process of adding a phosphate group (a molecule consisting of one phosphorus atom and four oxygen atoms) to a protein or other organic molecule, which is usually done by enzymes called kinases. This post-translational modification can change the function, localization, or activity of the target molecule, playing a crucial role in various cellular processes such as signal transduction, metabolism, and regulation of gene expression. Phosphorylation is reversible, and the removal of the phosphate group is facilitated by enzymes called phosphatases.

Western blotting is a laboratory technique used in molecular biology to detect and quantify specific proteins in a mixture of many different proteins. This technique is commonly used to confirm the expression of a protein of interest, determine its size, and investigate its post-translational modifications. The name "Western" blotting distinguishes this technique from Southern blotting (for DNA) and Northern blotting (for RNA).

The Western blotting procedure involves several steps:

1. Protein extraction: The sample containing the proteins of interest is first extracted, often by breaking open cells or tissues and using a buffer to extract the proteins.
2. Separation of proteins by electrophoresis: The extracted proteins are then separated based on their size by loading them onto a polyacrylamide gel and running an electric current through the gel (a process called sodium dodecyl sulfate-polyacrylamide gel electrophoresis or SDS-PAGE). This separates the proteins according to their molecular weight, with smaller proteins migrating faster than larger ones.
3. Transfer of proteins to a membrane: After separation, the proteins are transferred from the gel onto a nitrocellulose or polyvinylidene fluoride (PVDF) membrane using an electric current in a process called blotting. This creates a replica of the protein pattern on the gel but now immobilized on the membrane for further analysis.
4. Blocking: The membrane is then blocked with a blocking agent, such as non-fat dry milk or bovine serum albumin (BSA), to prevent non-specific binding of antibodies in subsequent steps.
5. Primary antibody incubation: A primary antibody that specifically recognizes the protein of interest is added and allowed to bind to its target protein on the membrane. This step may be performed at room temperature or 4°C overnight, depending on the antibody's properties.
6. Washing: The membrane is washed with a buffer to remove unbound primary antibodies.
7. Secondary antibody incubation: A secondary antibody that recognizes the primary antibody (often coupled to an enzyme or fluorophore) is added and allowed to bind to the primary antibody. This step may involve using a horseradish peroxidase (HRP)-conjugated or alkaline phosphatase (AP)-conjugated secondary antibody, depending on the detection method used later.
8. Washing: The membrane is washed again to remove unbound secondary antibodies.
9. Detection: A detection reagent is added to visualize the protein of interest by detecting the signal generated from the enzyme-conjugated or fluorophore-conjugated secondary antibody. This can be done using chemiluminescent, colorimetric, or fluorescent methods.
10. Analysis: The resulting image is analyzed to determine the presence and quantity of the protein of interest in the sample.

Western blotting is a powerful technique for identifying and quantifying specific proteins within complex mixtures. It can be used to study protein expression, post-translational modifications, protein-protein interactions, and more. However, it requires careful optimization and validation to ensure accurate and reproducible results.

Animal disease models are specialized animals, typically rodents such as mice or rats, that have been genetically engineered or exposed to certain conditions to develop symptoms and physiological changes similar to those seen in human diseases. These models are used in medical research to study the pathophysiology of diseases, identify potential therapeutic targets, test drug efficacy and safety, and understand disease mechanisms.

The genetic modifications can include knockout or knock-in mutations, transgenic expression of specific genes, or RNA interference techniques. The animals may also be exposed to environmental factors such as chemicals, radiation, or infectious agents to induce the disease state.

Examples of animal disease models include:

1. Mouse models of cancer: Genetically engineered mice that develop various types of tumors, allowing researchers to study cancer initiation, progression, and metastasis.
2. Alzheimer's disease models: Transgenic mice expressing mutant human genes associated with Alzheimer's disease, which exhibit amyloid plaque formation and cognitive decline.
3. Diabetes models: Obese and diabetic mouse strains like the NOD (non-obese diabetic) or db/db mice, used to study the development of type 1 and type 2 diabetes, respectively.
4. Cardiovascular disease models: Atherosclerosis-prone mice, such as ApoE-deficient or LDLR-deficient mice, that develop plaque buildup in their arteries when fed a high-fat diet.
5. Inflammatory bowel disease models: Mice with genetic mutations affecting intestinal barrier function and immune response, such as IL-10 knockout or SAMP1/YitFc mice, which develop colitis.

Animal disease models are essential tools in preclinical research, but it is important to recognize their limitations. Differences between species can affect the translatability of results from animal studies to human patients. Therefore, researchers must carefully consider the choice of model and interpret findings cautiously when applying them to human diseases.

A cell membrane, also known as the plasma membrane, is a thin semi-permeable phospholipid bilayer that surrounds all cells in animals, plants, and microorganisms. It functions as a barrier to control the movement of substances in and out of the cell, allowing necessary molecules such as nutrients, oxygen, and signaling molecules to enter while keeping out harmful substances and waste products. The cell membrane is composed mainly of phospholipids, which have hydrophilic (water-loving) heads and hydrophobic (water-fearing) tails. This unique structure allows the membrane to be flexible and fluid, yet selectively permeable. Additionally, various proteins are embedded in the membrane that serve as channels, pumps, receptors, and enzymes, contributing to the cell's overall functionality and communication with its environment.

'Tumor cells, cultured' refers to the process of removing cancerous cells from a tumor and growing them in controlled laboratory conditions. This is typically done by isolating the tumor cells from a patient's tissue sample, then placing them in a nutrient-rich environment that promotes their growth and multiplication.

The resulting cultured tumor cells can be used for various research purposes, including the study of cancer biology, drug development, and toxicity testing. They provide a valuable tool for researchers to better understand the behavior and characteristics of cancer cells outside of the human body, which can lead to the development of more effective cancer treatments.

It is important to note that cultured tumor cells may not always behave exactly the same way as they do in the human body, so findings from cell culture studies must be validated through further research, such as animal models or clinical trials.

Hematopoietic stem cells (HSCs) are immature, self-renewing cells that give rise to all the mature blood and immune cells in the body. They are capable of both producing more hematopoietic stem cells (self-renewal) and differentiating into early progenitor cells that eventually develop into red blood cells, white blood cells, and platelets. HSCs are found in the bone marrow, umbilical cord blood, and peripheral blood. They have the ability to repair damaged tissues and offer significant therapeutic potential for treating various diseases, including hematological disorders, genetic diseases, and cancer.

Extracellular signal-regulated mitogen-activated protein kinases (ERKs or Extracellular signal-regulated kinases) are a subfamily of the MAPK (mitogen-activated protein kinase) family, which are serine/threonine protein kinases that regulate various cellular processes such as proliferation, differentiation, migration, and survival in response to extracellular signals.

ERKs are activated by a cascade of phosphorylation events initiated by the binding of growth factors, hormones, or other extracellular molecules to their respective receptors. This activation results in the formation of a complex signaling pathway that involves the sequential activation of several protein kinases, including Ras, Raf, MEK (MAPK/ERK kinase), and ERK.

Once activated, ERKs translocate to the nucleus where they phosphorylate and activate various transcription factors, leading to changes in gene expression that ultimately result in the appropriate cellular response. Dysregulation of the ERK signaling pathway has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Zebrafish proteins refer to the diverse range of protein molecules that are produced by the organism Danio rerio, commonly known as the zebrafish. These proteins play crucial roles in various biological processes such as growth, development, reproduction, and response to environmental stimuli. They are involved in cellular functions like enzymatic reactions, signal transduction, structural support, and regulation of gene expression.

Zebrafish is a popular model organism in biomedical research due to its genetic similarity with humans, rapid development, and transparent embryos that allow for easy observation of biological processes. As a result, the study of zebrafish proteins has contributed significantly to our understanding of protein function, structure, and interaction in both zebrafish and human systems.

Some examples of zebrafish proteins include:

* Transcription factors that regulate gene expression during development
* Enzymes involved in metabolic pathways
* Structural proteins that provide support to cells and tissues
* Receptors and signaling molecules that mediate communication between cells
* Heat shock proteins that assist in protein folding and protect against stress

The analysis of zebrafish proteins can be performed using various techniques, including biochemical assays, mass spectrometry, protein crystallography, and computational modeling. These methods help researchers to identify, characterize, and understand the functions of individual proteins and their interactions within complex networks.

T-lymphocyte subsets refer to distinct populations of T-cells, which are a type of white blood cell that plays a central role in cell-mediated immunity. The two main types of T-lymphocytes are CD4+ and CD8+ cells, which are defined by the presence or absence of specific proteins called cluster differentiation (CD) molecules on their surface.

CD4+ T-cells, also known as helper T-cells, play a crucial role in activating other immune cells, such as B-lymphocytes and macrophages, to mount an immune response against pathogens. They also produce cytokines that help regulate the immune response.

CD8+ T-cells, also known as cytotoxic T-cells, directly kill infected cells or tumor cells by releasing toxic substances such as perforins and granzymes.

The balance between these two subsets of T-cells is critical for maintaining immune homeostasis and mounting effective immune responses against pathogens while avoiding excessive inflammation and autoimmunity. Therefore, the measurement of T-lymphocyte subsets is essential in diagnosing and monitoring various immunological disorders, including HIV infection, cancer, and autoimmune diseases.

According to the National Institutes of Health (NIH), stem cells are "initial cells" or "precursor cells" that have the ability to differentiate into many different cell types in the body. They can also divide without limit to replenish other cells for as long as the person or animal is still alive.

There are two main types of stem cells: embryonic stem cells, which come from human embryos, and adult stem cells, which are found in various tissues throughout the body. Embryonic stem cells have the ability to differentiate into all cell types in the body, while adult stem cells have more limited differentiation potential.

Stem cells play an essential role in the development and repair of various tissues and organs in the body. They are currently being studied for their potential use in the treatment of a wide range of diseases and conditions, including cancer, diabetes, heart disease, and neurological disorders. However, more research is needed to fully understand the properties and capabilities of these cells before they can be used safely and effectively in clinical settings.

A radioligand assay is a type of in vitro binding assay used in molecular biology and pharmacology to measure the affinity and quantity of a ligand (such as a drug or hormone) to its specific receptor. In this technique, a small amount of a radioactively labeled ligand, also known as a radioligand, is introduced to a sample containing the receptor of interest. The radioligand binds competitively with other unlabeled ligands present in the sample for the same binding site on the receptor. After allowing sufficient time for binding, the reaction is stopped, and the amount of bound radioligand is measured using a technique such as scintillation counting. The data obtained from this assay can be used to determine the dissociation constant (Kd) and maximum binding capacity (Bmax) of the receptor-ligand interaction, which are important parameters in understanding the pharmacological properties of drugs and other ligands.

Confocal microscopy is a powerful imaging technique used in medical and biological research to obtain high-resolution, contrast-rich images of thick samples. This super-resolution technology provides detailed visualization of cellular structures and processes at various depths within a specimen.

In confocal microscopy, a laser beam focused through a pinhole illuminates a small spot within the sample. The emitted fluorescence or reflected light from this spot is then collected by a detector, passing through a second pinhole that ensures only light from the focal plane reaches the detector. This process eliminates out-of-focus light, resulting in sharp images with improved contrast compared to conventional widefield microscopy.

By scanning the laser beam across the sample in a raster pattern and collecting fluorescence at each point, confocal microscopy generates optical sections of the specimen. These sections can be combined to create three-dimensional reconstructions, allowing researchers to study cellular architecture and interactions within complex tissues.

Confocal microscopy has numerous applications in medical research, including studying protein localization, tracking intracellular dynamics, analyzing cell morphology, and investigating disease mechanisms at the cellular level. Additionally, it is widely used in clinical settings for diagnostic purposes, such as analyzing skin lesions or detecting pathogens in patient samples.

Cell separation is a process used to separate and isolate specific cell types from a heterogeneous mixture of cells. This can be accomplished through various physical or biological methods, depending on the characteristics of the cells of interest. Some common techniques for cell separation include:

1. Density gradient centrifugation: In this method, a sample containing a mixture of cells is layered onto a density gradient medium and then centrifuged. The cells are separated based on their size, density, and sedimentation rate, with denser cells settling closer to the bottom of the tube and less dense cells remaining near the top.

2. Magnetic-activated cell sorting (MACS): This technique uses magnetic beads coated with antibodies that bind to specific cell surface markers. The labeled cells are then passed through a column placed in a magnetic field, which retains the magnetically labeled cells while allowing unlabeled cells to flow through.

3. Fluorescence-activated cell sorting (FACS): In this method, cells are stained with fluorochrome-conjugated antibodies that recognize specific cell surface or intracellular markers. The stained cells are then passed through a laser beam, which excites the fluorophores and allows for the detection and sorting of individual cells based on their fluorescence profile.

4. Filtration: This simple method relies on the physical size differences between cells to separate them. Cells can be passed through filters with pore sizes that allow smaller cells to pass through while retaining larger cells.

5. Enzymatic digestion: In some cases, cells can be separated by enzymatically dissociating tissues into single-cell suspensions and then using various separation techniques to isolate specific cell types.

These methods are widely used in research and clinical settings for applications such as isolating immune cells, stem cells, or tumor cells from biological samples.

Inflammation is a complex biological response of tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is characterized by the following signs: rubor (redness), tumor (swelling), calor (heat), dolor (pain), and functio laesa (loss of function). The process involves the activation of the immune system, recruitment of white blood cells, and release of inflammatory mediators, which contribute to the elimination of the injurious stimuli and initiation of the healing process. However, uncontrolled or chronic inflammation can also lead to tissue damage and diseases.

Endocytosis is the process by which cells absorb substances from their external environment by engulfing them in membrane-bound structures, resulting in the formation of intracellular vesicles. This mechanism allows cells to take up large molecules, such as proteins and lipids, as well as small particles, like bacteria and viruses. There are two main types of endocytosis: phagocytosis (cell eating) and pinocytosis (cell drinking). Phagocytosis involves the engulfment of solid particles, while pinocytosis deals with the uptake of fluids and dissolved substances. Other specialized forms of endocytosis include receptor-mediated endocytosis and caveolae-mediated endocytosis, which allow for the specific internalization of molecules through the interaction with cell surface receptors.

Gene expression is the process by which the information encoded in a gene is used to synthesize a functional gene product, such as a protein or RNA molecule. This process involves several steps: transcription, RNA processing, and translation. During transcription, the genetic information in DNA is copied into a complementary RNA molecule, known as messenger RNA (mRNA). The mRNA then undergoes RNA processing, which includes adding a cap and tail to the mRNA and splicing out non-coding regions called introns. The resulting mature mRNA is then translated into a protein on ribosomes in the cytoplasm through the process of translation.

The regulation of gene expression is a complex and highly controlled process that allows cells to respond to changes in their environment, such as growth factors, hormones, and stress signals. This regulation can occur at various stages of gene expression, including transcriptional activation or repression, RNA processing, mRNA stability, and translation. Dysregulation of gene expression has been implicated in many diseases, including cancer, genetic disorders, and neurological conditions.

"Nude mice" is a term used in the field of laboratory research to describe a strain of mice that have been genetically engineered to lack a functional immune system. Specifically, nude mice lack a thymus gland and have a mutation in the FOXN1 gene, which results in a failure to develop a mature T-cell population. This means that they are unable to mount an effective immune response against foreign substances or organisms.

The name "nude" refers to the fact that these mice also have a lack of functional hair follicles, resulting in a hairless or partially hairless phenotype. This feature is actually a secondary consequence of the same genetic mutation that causes their immune deficiency.

Nude mice are commonly used in research because their weakened immune system makes them an ideal host for transplanted tumors, tissues, and cells from other species, including humans. This allows researchers to study the behavior of these foreign substances in a living organism without the complication of an immune response. However, it's important to note that because nude mice lack a functional immune system, they must be kept in sterile conditions and are more susceptible to infection than normal mice.

Immunologic deficiency syndromes refer to a group of disorders characterized by defective functioning of the immune system, leading to increased susceptibility to infections and malignancies. These deficiencies can be primary (genetic or congenital) or secondary (acquired due to environmental factors, medications, or diseases).

Primary immunodeficiency syndromes (PIDS) are caused by inherited genetic mutations that affect the development and function of immune cells, such as T cells, B cells, and phagocytes. Examples include severe combined immunodeficiency (SCID), common variable immunodeficiency (CVID), Wiskott-Aldrich syndrome, and X-linked agammaglobulinemia.

Secondary immunodeficiency syndromes can result from various factors, including:

1. HIV/AIDS: Human Immunodeficiency Virus infection leads to the depletion of CD4+ T cells, causing profound immune dysfunction and increased vulnerability to opportunistic infections and malignancies.
2. Medications: Certain medications, such as chemotherapy, immunosuppressive drugs, and long-term corticosteroid use, can impair immune function and increase infection risk.
3. Malnutrition: Deficiencies in essential nutrients like protein, vitamins, and minerals can weaken the immune system and make individuals more susceptible to infections.
4. Aging: The immune system naturally declines with age, leading to an increased incidence of infections and poorer vaccine responses in older adults.
5. Other medical conditions: Chronic diseases such as diabetes, cancer, and chronic kidney or liver disease can also compromise the immune system and contribute to immunodeficiency syndromes.

Immunologic deficiency syndromes require appropriate diagnosis and management strategies, which may include antimicrobial therapy, immunoglobulin replacement, hematopoietic stem cell transplantation, or targeted treatments for the underlying cause.

Lymphocyte activation is the process by which B-cells and T-cells (types of lymphocytes) become activated to perform effector functions in an immune response. This process involves the recognition of specific antigens presented on the surface of antigen-presenting cells, such as dendritic cells or macrophages.

The activation of B-cells leads to their differentiation into plasma cells that produce antibodies, while the activation of T-cells results in the production of cytotoxic T-cells (CD8+ T-cells) that can directly kill infected cells or helper T-cells (CD4+ T-cells) that assist other immune cells.

Lymphocyte activation involves a series of intracellular signaling events, including the binding of co-stimulatory molecules and the release of cytokines, which ultimately result in the expression of genes involved in cell proliferation, differentiation, and effector functions. The activation process is tightly regulated to prevent excessive or inappropriate immune responses that can lead to autoimmunity or chronic inflammation.

Mononuclear leukocytes are a type of white blood cells (leukocytes) that have a single, large nucleus. They include lymphocytes (B-cells, T-cells, and natural killer cells), monocytes, and dendritic cells. These cells play important roles in the body's immune system, including defending against infection and disease, and participating in immune responses and surveillance. Mononuclear leukocytes can be found in the bloodstream as well as in tissues throughout the body. They are involved in both innate and adaptive immunity, providing specific and nonspecific defense mechanisms to protect the body from harmful pathogens and other threats.

B-lymphocytes, also known as B-cells, are a type of white blood cell that plays a key role in the immune system's response to infection. They are responsible for producing antibodies, which are proteins that help to neutralize or destroy pathogens such as bacteria and viruses.

When a B-lymphocyte encounters a pathogen, it becomes activated and begins to divide and differentiate into plasma cells, which produce and secrete large amounts of antibodies specific to the antigens on the surface of the pathogen. These antibodies bind to the pathogen, marking it for destruction by other immune cells such as neutrophils and macrophages.

B-lymphocytes also have a role in presenting antigens to T-lymphocytes, another type of white blood cell involved in the immune response. This helps to stimulate the activation and proliferation of T-lymphocytes, which can then go on to destroy infected cells or help to coordinate the overall immune response.

Overall, B-lymphocytes are an essential part of the adaptive immune system, providing long-lasting immunity to previously encountered pathogens and helping to protect against future infections.

CD (cluster of differentiation) antigens are cell-surface proteins that are expressed on leukocytes (white blood cells) and can be used to identify and distinguish different subsets of these cells. They are important markers in the field of immunology and hematology, and are commonly used to diagnose and monitor various diseases, including cancer, autoimmune disorders, and infectious diseases.

CD antigens are designated by numbers, such as CD4, CD8, CD19, etc., which refer to specific proteins found on the surface of different types of leukocytes. For example, CD4 is a protein found on the surface of helper T cells, while CD8 is found on cytotoxic T cells.

CD antigens can be used as targets for immunotherapy, such as monoclonal antibody therapy, in which antibodies are designed to bind to specific CD antigens and trigger an immune response against cancer cells or infected cells. They can also be used as markers to monitor the effectiveness of treatments and to detect minimal residual disease (MRD) after treatment.

It's important to note that not all CD antigens are exclusive to leukocytes, some can be found on other cell types as well, and their expression can vary depending on the activation state or differentiation stage of the cells.

Physiologic neovascularization is the natural and controlled formation of new blood vessels in the body, which occurs as a part of normal growth and development, as well as in response to tissue repair and wound healing. This process involves the activation of endothelial cells, which line the interior surface of blood vessels, and their migration, proliferation, and tube formation to create new capillaries. Physiologic neovascularization is tightly regulated by a balance of pro-angiogenic and anti-angiogenic factors, ensuring that it occurs only when and where it is needed. It plays crucial roles in various physiological processes, such as embryonic development, tissue regeneration, and wound healing.

HEK293 cells, also known as human embryonic kidney 293 cells, are a line of cells used in scientific research. They were originally derived from human embryonic kidney cells and have been adapted to grow in a lab setting. HEK293 cells are widely used in molecular biology and biochemistry because they can be easily transfected (a process by which DNA is introduced into cells) and highly express foreign genes. As a result, they are often used to produce proteins for structural and functional studies. It's important to note that while HEK293 cells are derived from human tissue, they have been grown in the lab for many generations and do not retain the characteristics of the original embryonic kidney cells.

Hematopoietic Stem Cell Mobilization is the process of mobilizing hematopoietic stem cells (HSCs) from the bone marrow into the peripheral blood. HSCs are immature cells that have the ability to differentiate into all types of blood cells, including red and white blood cells and platelets.

Mobilization is often achieved through the use of medications such as granulocyte-colony stimulating factor (G-CSF) or plerixafor, which stimulate the release of HSCs from the bone marrow into the peripheral blood. This allows for the collection of HSCs from the peripheral blood through a procedure called apheresis.

Mobilized HSCs can be used in stem cell transplantation procedures to reconstitute a patient's hematopoietic system after high-dose chemotherapy or radiation therapy. It is an important process in the field of regenerative medicine and has been used to treat various diseases such as leukemia, lymphoma, and sickle cell disease.

RNA interference (RNAi) is a biological process in which RNA molecules inhibit the expression of specific genes. This process is mediated by small RNA molecules, including microRNAs (miRNAs) and small interfering RNAs (siRNAs), that bind to complementary sequences on messenger RNA (mRNA) molecules, leading to their degradation or translation inhibition.

RNAi plays a crucial role in regulating gene expression and defending against foreign genetic elements, such as viruses and transposons. It has also emerged as an important tool for studying gene function and developing therapeutic strategies for various diseases, including cancer and viral infections.

Anti-HIV agents are a class of medications specifically designed to treat HIV (Human Immunodeficiency Virus) infection. These drugs work by interfering with various stages of the HIV replication cycle, preventing the virus from infecting and killing CD4+ T cells, which are crucial for maintaining a healthy immune system.

There are several classes of anti-HIV agents, including:

1. Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs): These drugs act as faulty building blocks that the virus incorporates into its genetic material, causing the replication process to halt. Examples include zidovudine (AZT), lamivudine (3TC), and tenofovir.
2. Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs): These medications bind directly to the reverse transcriptase enzyme, altering its shape and preventing it from functioning properly. Examples include efavirenz, nevirapine, and rilpivirine.
3. Protease Inhibitors (PIs): These drugs target the protease enzyme, which is responsible for cleaving viral polyproteins into functional components. By inhibiting this enzyme, PIs prevent the formation of mature, infectious virus particles. Examples include atazanavir, darunavir, and lopinavir.
4. Integrase Strand Transfer Inhibitors (INSTIs): These medications block the integrase enzyme, which is responsible for inserting the viral genetic material into the host cell's DNA. By inhibiting this step, INSTIs prevent the virus from establishing a permanent infection within the host cell. Examples include raltegravir, dolutegravir, and bictegravir.
5. Fusion/Entry Inhibitors: These drugs target different steps of the viral entry process, preventing HIV from infecting CD4+ T cells. Examples include enfuvirtide (T-20), maraviroc, and ibalizumab.
6. Post-Attachment Inhibitors: This class of medications prevents the virus from attaching to the host cell's receptors, thereby inhibiting infection. Currently, there is only one approved post-attachment inhibitor, fostemsavir.

Combination therapy using multiple classes of antiretroviral drugs has been shown to effectively suppress viral replication and improve clinical outcomes in people living with HIV. Regular adherence to the prescribed treatment regimen is crucial for maintaining an undetectable viral load and reducing the risk of transmission.

Pathologic neovascularization is the abnormal growth of new blood vessels in previously avascular tissue or excessive growth within existing vasculature, which occurs as a result of hypoxia, inflammation, or angiogenic stimuli. These newly formed vessels are often disorganized, fragile, and lack proper vessel hierarchy, leading to impaired blood flow and increased vascular permeability. Pathologic neovascularization can be observed in various diseases such as cancer, diabetic retinopathy, age-related macular degeneration, and chronic inflammation. This process contributes to disease progression by promoting tumor growth, metastasis, and edema formation, ultimately leading to tissue damage and organ dysfunction.

Apoptosis is a programmed and controlled cell death process that occurs in multicellular organisms. It is a natural process that helps maintain tissue homeostasis by eliminating damaged, infected, or unwanted cells. During apoptosis, the cell undergoes a series of morphological changes, including cell shrinkage, chromatin condensation, and fragmentation into membrane-bound vesicles called apoptotic bodies. These bodies are then recognized and engulfed by neighboring cells or phagocytic cells, preventing an inflammatory response. Apoptosis is regulated by a complex network of intracellular signaling pathways that involve proteins such as caspases, Bcl-2 family members, and inhibitors of apoptosis (IAPs).

CD34 is a type of antigen that is found on the surface of certain cells in the human body. Specifically, CD34 antigens are present on hematopoietic stem cells, which are immature cells that can develop into different types of blood cells. These stem cells are found in the bone marrow and are responsible for producing red blood cells, white blood cells, and platelets.

CD34 antigens are a type of cell surface marker that is used in medical research and clinical settings to identify and isolate hematopoietic stem cells. They are also used in the development of stem cell therapies and transplantation procedures. CD34 antigens can be detected using various laboratory techniques, such as flow cytometry or immunohistochemistry.

It's important to note that while CD34 is a useful marker for identifying hematopoietic stem cells, it is not exclusive to these cells and can also be found on other cell types, such as endothelial cells that line blood vessels. Therefore, additional markers are often used in combination with CD34 to more specifically identify and isolate hematopoietic stem cells.

Protein-kinase B, also known as AKT, is a group of intracellular proteins that play a crucial role in various cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration. The AKT family includes three isoforms: AKT1, AKT2, and AKT3, which are encoded by the genes PKBalpha, PKBbeta, and PKBgamma, respectively.

Proto-oncogene proteins c-AKT refer to the normal, non-mutated forms of these proteins that are involved in the regulation of cell growth and survival under physiological conditions. However, when these genes are mutated or overexpressed, they can become oncogenes, leading to uncontrolled cell growth and cancer development.

Activation of c-AKT occurs through a signaling cascade that begins with the binding of extracellular ligands such as insulin-like growth factor 1 (IGF-1) or epidermal growth factor (EGF) to their respective receptors on the cell surface. This triggers a series of phosphorylation events that ultimately lead to the activation of c-AKT, which then phosphorylates downstream targets involved in various cellular processes.

In summary, proto-oncogene proteins c-AKT are normal intracellular proteins that play essential roles in regulating cell growth and survival under physiological conditions. However, their dysregulation can contribute to cancer development and progression.

Bone marrow is the spongy tissue found inside certain bones in the body, such as the hips, thighs, and vertebrae. It is responsible for producing blood-forming cells, including red blood cells, white blood cells, and platelets. There are two types of bone marrow: red marrow, which is involved in blood cell production, and yellow marrow, which contains fatty tissue.

Red bone marrow contains hematopoietic stem cells, which can differentiate into various types of blood cells. These stem cells continuously divide and mature to produce new blood cells that are released into the circulation. Red blood cells carry oxygen throughout the body, white blood cells help fight infections, and platelets play a crucial role in blood clotting.

Bone marrow also serves as a site for immune cell development and maturation. It contains various types of immune cells, such as lymphocytes, macrophages, and dendritic cells, which help protect the body against infections and diseases.

Abnormalities in bone marrow function can lead to several medical conditions, including anemia, leukopenia, thrombocytopenia, and various types of cancer, such as leukemia and multiple myeloma. Bone marrow aspiration and biopsy are common diagnostic procedures used to evaluate bone marrow health and function.

HL-60 cells are a type of human promyelocytic leukemia cell line that is commonly used in scientific research. They are named after the hospital where they were first isolated, the Hospital of the University of Pennsylvania (HUP) and the 60th culture attempt to grow these cells.

HL-60 cells have the ability to differentiate into various types of blood cells, such as granulocytes, monocytes, and macrophages, when exposed to certain chemical compounds or under specific culturing conditions. This makes them a valuable tool for studying the mechanisms of cell differentiation, proliferation, and apoptosis (programmed cell death).

HL-60 cells are also often used in toxicity studies, drug discovery and development, and research on cancer, inflammation, and infectious diseases. They can be easily grown in the lab and have a stable genotype, making them ideal for use in standardized experiments and comparisons between different studies.

Calcium is an essential mineral that is vital for various physiological processes in the human body. The medical definition of calcium is as follows:

Calcium (Ca2+) is a crucial cation and the most abundant mineral in the human body, with approximately 99% of it found in bones and teeth. It plays a vital role in maintaining structural integrity, nerve impulse transmission, muscle contraction, hormonal secretion, blood coagulation, and enzyme activation.

Calcium homeostasis is tightly regulated through the interplay of several hormones, including parathyroid hormone (PTH), calcitonin, and vitamin D. Dietary calcium intake, absorption, and excretion are also critical factors in maintaining optimal calcium levels in the body.

Hypocalcemia refers to low serum calcium levels, while hypercalcemia indicates high serum calcium levels. Both conditions can have detrimental effects on various organ systems and require medical intervention to correct.

Cell survival refers to the ability of a cell to continue living and functioning normally, despite being exposed to potentially harmful conditions or treatments. This can include exposure to toxins, radiation, chemotherapeutic drugs, or other stressors that can damage cells or interfere with their normal processes.

In scientific research, measures of cell survival are often used to evaluate the effectiveness of various therapies or treatments. For example, researchers may expose cells to a particular drug or treatment and then measure the percentage of cells that survive to assess its potential therapeutic value. Similarly, in toxicology studies, measures of cell survival can help to determine the safety of various chemicals or substances.

It's important to note that cell survival is not the same as cell proliferation, which refers to the ability of cells to divide and multiply. While some treatments may promote cell survival, they may also inhibit cell proliferation, making them useful for treating diseases such as cancer. Conversely, other treatments may be designed to specifically target and kill cancer cells, even if it means sacrificing some healthy cells in the process.

Lymphocytes are a type of white blood cell that is an essential part of the immune system. They are responsible for recognizing and responding to potentially harmful substances such as viruses, bacteria, and other foreign invaders. There are two main types of lymphocytes: B-lymphocytes (B-cells) and T-lymphocytes (T-cells).

B-lymphocytes produce antibodies, which are proteins that help to neutralize or destroy foreign substances. When a B-cell encounters a foreign substance, it becomes activated and begins to divide and differentiate into plasma cells, which produce and secrete large amounts of antibodies. These antibodies bind to the foreign substance, marking it for destruction by other immune cells.

T-lymphocytes, on the other hand, are involved in cell-mediated immunity. They directly attack and destroy infected cells or cancerous cells. T-cells can also help to regulate the immune response by producing chemical signals that activate or inhibit other immune cells.

Lymphocytes are produced in the bone marrow and mature in either the bone marrow (B-cells) or the thymus gland (T-cells). They circulate throughout the body in the blood and lymphatic system, where they can be found in high concentrations in lymph nodes, the spleen, and other lymphoid organs.

Abnormalities in the number or function of lymphocytes can lead to a variety of immune-related disorders, including immunodeficiency diseases, autoimmune disorders, and cancer.

Lymphoid tissue is a specialized type of connective tissue that is involved in the immune function of the body. It is composed of lymphocytes (a type of white blood cell), which are responsible for producing antibodies and destroying infected or cancerous cells. Lymphoid tissue can be found throughout the body, but it is particularly concentrated in certain areas such as the lymph nodes, spleen, tonsils, and Peyer's patches in the small intestine.

Lymphoid tissue provides a site for the activation, proliferation, and differentiation of lymphocytes, which are critical components of the adaptive immune response. It also serves as a filter for foreign particles, such as bacteria and viruses, that may enter the body through various routes. The lymphatic system, which includes lymphoid tissue, helps to maintain the health and integrity of the body by protecting it from infection and disease.

Gene knockdown techniques are methods used to reduce the expression or function of specific genes in order to study their role in biological processes. These techniques typically involve the use of small RNA molecules, such as siRNAs (small interfering RNAs) or shRNAs (short hairpin RNAs), which bind to and promote the degradation of complementary mRNA transcripts. This results in a decrease in the production of the protein encoded by the targeted gene.

Gene knockdown techniques are often used as an alternative to traditional gene knockout methods, which involve completely removing or disrupting the function of a gene. Knockdown techniques allow for more subtle and reversible manipulation of gene expression, making them useful for studying genes that are essential for cell survival or have redundant functions.

These techniques are widely used in molecular biology research to investigate gene function, genetic interactions, and disease mechanisms. However, it is important to note that gene knockdown can have off-target effects and may not completely eliminate the expression of the targeted gene, so results should be interpreted with caution.

... is one of several chemokine co-receptors that HIV can use to infect CD4+ T cells. HIV isolates that use CXCR4 are ... CXCR4 dimerization is dynamic and increases with concentration. Drugs that block the CXCR4 receptor appear to be capable of " ... "Chemokine Receptors: CXCR4". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... The protein is a CXC chemokine receptor. CXCR-4 is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 ...
A CXCR4 antagonist is a substance which blocks the CXCR4 receptor and prevent its activation. Blocking the receptor stops the ... The CXCR4 receptor has been targeted by antagonistic substances since being identified as a co-receptor in HIV and assisting ... Knight, James C (2012). "Nuclear (PET/SPECT) and optical imaging probes targeting the CXCR4 chemokine receptor". MedChemComm. 3 ... Macrocyclic ligands have been utilised as CXCR4 antagonists. Plerixafor is an example of a CXCR4 antagonist, and has approvals ...
The majority of HIV strains use the CCR5 receptor. HIV-2 strains can also use the CXCR4 receptor though the CCR5 receptor is ... Both the CCR5 and the CXCR4 co-receptors are seven-trans-membrane (7TM) G protein-coupled receptors. Different strains of HIV ... The CD receptor family typically act as co-receptors, illustrated by the classic example of CD4 acting as a co-receptor to the ... A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to ...
September 2009). "A functional heteromeric MIF receptor formed by CD74 and CXCR4". FEBS Letters. 583 (17): 2749-57. doi:10.1016 ... Farr L, Ghosh S, Moonah S (2020). "Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair ... Farr L, Ghosh S, Moonah S (2020). "Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair ... Farr L, Ghosh S, Moonah S (2020). "Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair ...
"Expression of functional CXCR4 chemokine receptors on human colonic epithelial cells". The Journal of Clinical Investigation. ... These receptors belongs to the G protein-coupled seven-transmembrane receptors. CCL7 can also interact with cell surface ... C-C CKR1, a receptor for macrophage inflammatory protein-1 alpha/Rantes, is also a functional receptor for MCP3". The Journal ... "Chemokine receptor responses on T cells are achieved through regulation of both receptor expression and signaling". Journal of ...
Mostashari-Rad T, Arian R, Mehridehnavi A, Fassihi A, Ghasemi F (June 13, 2019). "Study of CXCR4 chemokine receptor inhibitors ... However, dealing with receptor flexibility in docking methodologies is still a thorny issue. The main reason behind this ... If the protein is a receptor, ligand binding may result in agonism or antagonism. Docking is most commonly used in the field of ... In the case of G protein-coupled receptors (GPCRs), which are targets of more than 30% of marketed drugs, molecular docking led ...
CXCR4, previously called LESTR or fusin, is the receptor for CXCL12. This CXCL12-CXCR4 interaction used to be considered ... For instance, blocking CXCR4, the receptor for CXCL12, with Plerixafor (AMD-3100) increased the effectiveness of combretastatin ... it was suggested that CXCL12 may also bind the CXCR7 receptor (now called ACKR3). By blocking CXCR4, a major coreceptor for HIV ... "Clinical importance and therapeutic implications of the pivotal CXCL12-CXCR4 (chemokine ligand-receptor) interaction in cancer ...
Ghosh S, Preet A, Groopman JE, Ganju RK (July 2006). "Cannabinoid receptor CB2 modulates the CXCL12/CXCR4-mediated chemotaxis ... Its affinity for CB2 receptors is 13.8 nM, while its affinity for CB1 is 383 nM, meaning that it binds almost 28 times more ... In the United States, all CB1 receptor agonists of the 3-(1-naphthoyl)indole class such as JWH-015 are Schedule I Controlled ... Marriott KS, Huffman JW (2008). "Recent advances in the development of selective ligands for the cannabinoid CB(2) receptor". ...
Lee, JH; Park, JW; Kim, SW; Park, J; Park, TS (15 December 2017). "C-X-C chemokine receptor type 4 (CXCR4) is a key receptor ... the PGCs express two CXCR4 transmembrane receptor proteins. The signaling system involving this protein and its ligand, Sdf1, ... The CXCR4/Sdf1 system is also used, though may not be the only method necessary. In the mouse, primordial germ cells (PGCs) ... There is also evidence for the CXCR4/Sdf1 system in frogs.[citation needed] In birds, the PGCs arise from the epiblast and ...
CCR5 and CXCR4 are the main receptors involved in the HIV entry process. These receptors belong to the seven transmembrane G- ... R5 strain is when the virus uses the co-receptor CCR5 and X4 strain is when it uses CXCR4. The location of CCR5 receptors at ... CCR5 receptor antagonists are a class of small molecules that antagonize the CCR5 receptor. The C-C motif chemokine receptor ... As mentioned, the CCR5 receptor is a G-protein coupled receptor (GPCR). Before the discovery of CCR5's role in HIV infection, ...
Moreover, inhibition of the CXCR4 receptor reduced metastatic potential without altering tumorigenic capacity. Epithelial- ... Leptin receptor (LEPR) is a type I cytokine receptor for the fat associate hormone leptin, which plays an important role in ... The cell surface receptor interleukin-3 receptor-alpha (CD123) is overexpressed on CD34+CD38- leukemic stem cells (LSCs) in ... In the invasive edge of pancreatic carcinoma, a subset of CD133+CXCR4+ (receptor for CXCL12 chemokine also known as a SDF1 ...
CXCR4 and CCR5). They are G protein coupled receptors. TGF-beta receptor family, which are Serine/threonine kinase receptors. ... Cytokine receptors are receptors that bind to cytokines. In recent years, the cytokine receptors have come to demand the ... Includes the TGF beta receptors Cytokine receptors may be both membrane-bound and soluble. Soluble cytokine receptors are ... Soluble cytokine receptors typically consist of the extracellular portions of membrane-bound receptors. . STAT protein Brooks, ...
"The chemokine SDF-1alpha triggers CXCR4 receptor dimerization and activates the JAK/STAT pathway". FASEB Journal. 13 (13): 1699 ... March 1996). "Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 ... March 1996). "Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 ... In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and ...
1999). "Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4". Developmental Biology. 213 (2): 442- ... the interaction between the chemokine CXCL12 expressed by stromal cells and its receptor CXCR4 expressed on HSCs has been ... 1991). "The kit receptor and its ligand, steel factor, as regulators of hematopoiesis". Cancer Cells. 3 (12): 480-487. PMID ... It has also been found that calcium ions can act as chemotactic signals to HSCs via the G protein-coupled receptor (GPCR) ...
HIV infects T-helper cells by binding to the CD4 receptor and the co-receptor CCR5 or CXCR4. CD4-Ig binds to the viral envelope ... The CD4 receptor is used as a primary receptor by HIV to attach to the surface of target cells. HIV then uses a co-receptor, ... "Inhibition of T-tropic HIV Strains by Selective Antagonization of the Chemokine Receptor CXCR4". Journal of Experimental ... The protein is a fusion of the extracellular domain of the CD4 receptor and the Fc domain of human immunoglobulin G (IgG), the ...
M-tropic HIV-1 isolates that use only the CCR5 receptor are termed R5; those that use only CXCR4 are termed X4, and those that ... on the HIV viral envelope and both CD4 and a chemokine co-receptor (generally either CCR5 or CXCR4, but others are known to ... replicate in primary CD4+ T cells as well as in macrophages and use the α-chemokine receptor, CXCR4, for entry. Dual-tropic HIV ... exposing the chemokine receptor binding domains of gp120 and allowing them to interact with the target chemokine receptor. This ...
"Leukocyte analysis from WHIM syndrome patients reveals a pivotal role for GRK3 in CXCR4 signaling". The Journal of Clinical ... active receptor also enables receptor signaling through arrestin partner proteins. As a result, the G protein-coupled receptors ... "Orphanin FQ/nociceptin-mediated desensitization of opioid receptor-like 1 receptor and mu opioid receptors involves protein ... G protein-coupled receptor kinases phosphorylate activated G protein-coupled receptors, which promotes the binding of an ...
CXCR4 (also known as fusin) is the receptor for a chemokine known as CXCL12 (or SDF-1) and, as with CCR5, is utilized by HIV-1 ... "Chemokine Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. ( ... They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven ... However, CXCR6 is more closely related in structure to CC chemokine receptors than to other CXC chemokine receptors. ACKR3 was ...
"Turning Receptors On and Off with Intracellular Pepducins: New Insights into G-protein Coupled Receptor Drug Development". J ... A CXCR4 agonist pepducin mobilizes bone marrow hematopoietic cells. A PAR1 pepducin, PZ-128, has successfully completed phase I ... "Discovery of a CXCR4 agonist pepducin that mobilizes bone marrow hematopoietic cells". 2010. Archived from the original on 2011 ... Pepducins employ lipidated fragments of intracellular G protein-coupled receptor loops to modulate GPCR action in targeted cell ...
"Gambogic acid inhibits multiple myeloma mediated osteoclastogenesis through suppression of chemokine receptor CXCR4 signaling ... 2005). "A role for transferrin receptor in triggering apoptosis when targeted with gambogic acid". Proceedings of the National ... Gambogic acid inhibits such osteoclastogenesis by inhibiting CXCR4 signaling pathways. Gambogic acid has also been found to ... a novel ligand for transferrin receptor, potentiates TNF-induced apoptosis through modulation of the nuclear factor-kappaB ...
"The ubiquitin ligase deltex-3l regulates endosomal sorting of the G protein-coupled receptor CXCR4". Mol. Biol. Cell. 25 (12): ...
"Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease". Nat. ... A gain-of-function mutation resulting in a truncated form of CXCR4 is believed to be its cause. The truncated form of the ... receptor has a 2-fold increase in G-protein coupled intracellular signalling, and this mutation of the receptor can be ...
A focus on the CCR5 co-receptor as a potential target for anti-HIV medications began in 1996 with the discovery of CCR5-Δ32, or ... X4 virus, or T-tropic HIV-1, targets T-cells and uses CXCR4 as the coreceptor. Dual-tropic strains of HIV-1, which utilize both ... However, viral changes from CCR5 to CXCR4 coreceptor usage have been associated with a faster rate of CD4+ T-cell loss, rapid ... The two coreceptors involved in the entry of HIV-1, CCR5 and CXCR4, belong to the larger family of 7-transmembrane segment (7TM ...
It may be mediated by interaction through CXCR4 (CD184) the receptor for CXC Chemokines (e.g., SDF1) and α4β1 integrins. ... Burger JA, Spoo A, Dwenger A, Burger M, Behringer D (August 2003). "CXCR4 chemokine receptors (CD184) and alpha4beta1 integrins ...
... results from autosomal dominant mutations in the gene for the chemokine receptor, CXCR4, resulting in a carboxy- ... 2011). "AMD3100 is a potent antagonist at CXCR4(R334X), a hyperfunctional mutant chemokine receptor and cause of WHIM syndrome ... May 2003). "Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency ... The truncation of the receptor protein results in the inability of downregulation after stimulation. Thus, the receptor remain ...
There has been some inquiry into the relationship between HHV-7 and HIV-1 co-receptors CXCR4 and CCR5. During infection, HHV-7 ... This information indicates that CXCR4 and CCR5 are not essential receptor proteins for HHV-7 infection. The trademark ... Despite this, HHV-7 may be able to enter cells that do not express the CD46 receptor. About a week after HHV-7 has infected a ... a CXCR4 antagonist that was effective against HIV was shown to be ineffective at inhibiting HHV-7. ...
... a selective CXCR4 receptor inhibitor, in HIV-1 infection". Journal of Acquired Immune Deficiency Syndromes. 37 (2): 1253-62. ...
For example, suppression of chemokine receptors (CXCR4 and CCR5) on host cells can prevent HIV viral entry. While traditional ... which cause the release pattern recognition receptors (PRRs). These receptors help in labeling which pathogens are viruses, ... Lapteva N, Yang AG, Sanders DE, Strube RW, Chen SY (January 2005). "CXCR4 knockdown by small interfering RNA abrogates breast ... Crowe S (2003). "Suppression of chemokine receptor expression by RNA interference allows for inhibition of HIV-1 replication, ...
"Human B cells immortalized with Epstein-Barr virus upregulate CCR6 and CCR10 and downregulate CXCR4 and CXCR5". Journal of ... The protein encoded by this gene is a member of the G protein-coupled receptor family. This receptor was identified as a gene ... C-C chemokine receptor type 7 is a protein that in humans is encoded by the CCR7 gene. Two ligands have been identified for ... The receptor is expressed mostly on adaptive immune cell types, namely thymocytes, naive T and B cells, regulatory T cells, ...
CXCR4 and CXCR7, can be used as molecular prognosis factors. People who express low levels of both chemokine receptors have the ... Retrospective research showed that two chemokine receptors, ...
How CXCR4 signaling integrates with other relevant oncogenic transduction pathways and the role of GPCR regulatory mechanisms ... The CXCL12 chemokine receptor CXCR4 belongs to the GPCR superfamily and is often overexpressed in cancer, being involved in ... Recent data indicate concurrent upregulation in certain tumors of CXCR4, EGF receptor (EGFR), and G protein-coupled receptor ... Modulation of CXCR4-Mediated Gi1 Activation by EGF Receptor and GRK2 ACS Pharmacol Transl Sci. 2020 Apr 27;3(4):627-634. doi: ...
... ... Free subject headings]: B-cell antigen receptor , IgD , CXCR4 , cytoskeleton , signaling , baff-r , actin cytoskeleton , t- ...
CXCR4 is one of several chemokine co-receptors that HIV can use to infect CD4+ T cells. HIV isolates that use CXCR4 are ... CXCR4 dimerization is dynamic and increases with concentration. Drugs that block the CXCR4 receptor appear to be capable of " ... "Chemokine Receptors: CXCR4". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... The protein is a CXC chemokine receptor. CXCR-4 is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 ...
The Effect of Small Molecule 390 on CXCR4 Receptors. ... of the CXCR4 receptor. Because it binds to the receptor and ... Cxcr4. Novel Molecule 390. Receptor. Sdf-1. Stem Cells Article Download: The Effect of Small Molecule 390 on CXCR4 Receptors. ... The Effect of Small Molecule 390 on CXCR4 Receptors. ABSTRACT. CXCR4 is the chemokine receptor which aids in chemotaxis of stem ... As a CXC-type chemokine receptor, or a receptor that responds to CXC chemokines, CXCR4 aids in cell chemotaxis when it is ...
i,CXCR4,/i, mutation status did not affect treatment response. ... Receptors, CXCR4 / genetics * Sulfonamides / adverse effects * ... CXCR4 mutations did not affect treatment response or progression-free survival. The only recurring grade ≥ 3 treatment-related ... and 17 carried CXCR4 mutations. The median time to minor and major responses was 1.9 and 5.1 months, respectively. Previous ...
Chemokine receptors (e.g., CXCR4, CCR6, CCR7, CCR9). Stomach, lung, kidney, colon, breast. [86-91]. ...
... in the chemokine receptor CXCR4 detected in human cancer cells enhances migration. The chemokine receptor CXCR4 is widely ... Cxc Chemokine Receptor, Cxcl12, G-Protein Coupled Receptor (gpcr), Gi Subfamily, Melanoma, Perk, Chemokine Receptor Cxcr4, ... Ligand-Based NMR Study of C-X-C Chemokine Receptor Type 4 (CXCR4)-Ligand Interactions on Living Cancer Cells (1148 views). J ... A point mutation (G574A) in the chemokine receptor CXCR4 detected in human cancer cells enhances migration. Filter those ...
Engineered CXCL12 ligand-CXCR4 receptor signaling complexes for enhanced chemotaxix Method for engineering very sensitive and ... Method for engineering peptide-receptor signaling complexes for enhanced chemotaxis Method for engineering very sensitive and ...
The CXCR4 gene provides instructions for making a receptor protein that spans the outer membrane of cells, specifically white ... The CXCR4 receptor is also involved in the movement (migration) of cells. Cells that have the CXCR4 protein in their membrane ... The CXCR4 gene provides instructions for making a receptor protein that spans the outer membrane of cells, specifically white ... URL of this page: https://medlineplus.gov/genetics/gene/cxcr4/ CXCR4 gene. C-X-C motif chemokine receptor 4 ...
Interferon-γ increases expression of chemokine receptors CCR1, CCR3, and CCR5, but not CXCR4 in monocytoid U937 cells. Blood. ... Interferon-γ increases expression of chemokine receptors CCR1, CCR3, and CCR5, but not CXCR4 in monocytoid U937 cells. In: ... Interferon-γ increases expression of chemokine receptors CCR1, CCR3, and CCR5, but not CXCR4 in monocytoid U937 cells. / Zella ... Dive into the research topics of Interferon-γ increases expression of chemokine receptors CCR1, CCR3, and CCR5, but not CXCR4 ...
Chemokine receptor CXCR4 and early-stage non-small cell lung tumor: design of appearance and relationship with result. Ann ... Hartmann TN, Burger JA, Glodek A, Fujii N, Burger M. CXCR4 chemokine receptor and integrin signaling co-operate in mediating ... Introduction For most tumors, the overexpression from the chemokine receptor CXCR4. Introduction For most tumors, the ... Weitzenfeld P, Ben-Baruch A. The chemokine program, and its own CCR5 and CXCR4 receptors, as potential goals for individualized ...
The chemokine CXCL12 (stromal cell-derived factor-1, SDF-1) and its receptor CXCR4. * Post author By cellsignaling ... The chemokine CXCL12 (stromal cell-derived factor-1, SDF-1) and its receptor CXCR4 play a major role in tumor initiation, ... or to non-peptide receptor-selective antagonists AMD3100 (1?M; g) or CCX733 (0.1?M; h) receptors were rapidly internalized ... Without activation, receptors were scattered alone or lay in close proximity at the cell surface. b For secondary antibody ...
RT-PCR analysis indicated that the predominant receptor expressed on RPE cells was CXCR4. The level of CXCR4 mRNA expression, ... RT-PCR analysis indicated that the predominant receptor expressed on RPE cells was CXCR4. The level of CXCR4 mRNA expression, ... RT-PCR analysis indicated that the predominant receptor expressed on RPE cells was CXCR4. The level of CXCR4 mRNA expression, ... RT-PCR analysis indicated that the predominant receptor expressed on RPE cells was CXCR4. The level of CXCR4 mRNA expression, ...
CCR5 and CXCR4 Co-receptors in HIV Infection. This article examined the central role played by co-receptor expression and usage ... The review contains a discussion of the HIV-1 phenotypic variants defined by their use of the CCR5 or CXCR4 co-receptors. How ... The review also contains a consideration of the possible outcomes of the use of co-receptor antagonists as drugs to treat HIV-1 ... The CCR5 and CXCR4 coreceptors-central to understanding the transmission and pathogenesis of human immunodeficiency virus type ...
Aberrant expression and activity of G proteins and G-protein-coupled receptors (GPCRs) are frequently associated with ... Aberrant expression and activity of G proteins and G-protein-coupled receptors (GPCRs) are frequently associated with ... Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 330, 1066-1071 (2010). ... EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature 402, 884- ...
A similar study demonstrated that MSCs expressing C-X-C chemokine receptor type 4 (CXCR4) had greater hepatic colonizability ... Deng C, Qin A, Zhao W, Feng T, Shi C, Liu T. Up-regulation of CXCR4 in rat umbilical mesenchymal stem cells induced by serum ... Interleukin-1 receptor antagonist (IL-1Ra) and IL-1Ra producing mesenchymal stem cells as modulators of diabetogenesis. ... Proteomic analysis showed that HPL-CM contained anti-inflammatory factors, including IL-10, IL-1-receptor antagonist (IL-1ra), ...
C-X-C chemokine receptor 2 (CXCR2) is a chemotactic receptor that is critical in neutrophil mobilization from bone marrow to ... We have previously reported that a single nucleotide polymorphism (SNP) in leptin receptor (LEPR), present in up to 50% of ... We have previously reported that a single nucleotide polymorphism (SNP) in leptin receptor (LEPR), present in up to 50% of ... is a chemotactic receptor that is critical in neutrophil mobilization from bone marrow to blood and tissue sites. ...
Human CXCR4 (Chemokine C-X-C-Motif Receptor 4) ELISA Kit , G-EC-03803 ... Rat SCARB1 (Scavenger receptor class B member 1) ELISA Kit , G-EC-05852 Rat SCARB1 (Scavenger receptor class B member 1) ELISA ... Rat TLR-2 (Toll-like Receptor 2) ELISA Kit , G-EC-05655 Rat TLR-2 (Toll-like Receptor 2) ELISA Kit , G-EC-05655 , Gentaur Elisa ... Rat TLR4 (Toll-Like Receptor 4) ELISA Kit , G-EC-05714 Rat TLR4 (Toll-Like Receptor 4) ELISA Kit , G-EC-05714 , Gentaur Elisa ...
View gene expression results for Cxcr4 with assay type, age, structure, image, mutant allele, reference ... Cxcr4 C-X-C motif chemokine receptor 4 MGI:109563 .yui-skin-sam .yui-dt th{ background:url(https://www.informatics.jax.org/ ...
The chemokine receptors CCR5 and CXCR4 belong to the class of 7 transmembrane G-protein-coupled receptors, and their natural ... CCR5 and CXCR4 are the 2 main co-receptors essential for HIV entry. Macrophages in chancroid lesions have significantly ... Together with the disruption of mucosal and skin barriers, the presence of cells with up-regulated HIV-1 co-receptors in H ... increased expression of CCR5 and CXCR4 compared with peripheral blood cells, and CD4 T cells have significant up-regulation of ...
CXCR4 and ACKR3. Ligand/Receptor CXCR4. Cell Type Dendritic cells, Endothelial cells, Epithelial cells, Fibroblasts Biology ... SDF-1/CXCR4 pair plays a role in the mobilization of CD34+ progenitors to peripheral blood. SDF-1 is important in morphogenesis ... The SDF-1/CXCR4 pair plays a key role in maintaining proliferation and survival of bone marrow stem cell subpopulations under ...
CXCR4 is one of several chemokine receptors that HIV can use to infect CD4+ T cells. HIV isolates that use CXCR4 are ... "Chemokine Receptors: CXCR4". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in ... a surface polarization of the CXCR4 receptors suggesting that this receptor is implicated in the adhesion phase of human ...
Cxcr4. C-X-C motif chemokine receptor 4. ISO. CTD Direct Evidence: marker/mechanism. CTD. PMID:30818366. NCBI chr13:40,077,976 ... leukotriene B4 receptor. ISO. CTD Direct Evidence: marker/mechanism. CTD. PMID:30818366. NCBI chr15:29,263,199...29,265,716 ...
EpiCor caused strong inhibition of Fucoidan-mediated expression of the chemokine receptors CXCR4 and CCR9 on PBMC. This ... An antiinflammatory immunogen from yeast culture induces activation and alters chemokine receptor expression on human natural ... quantities of IL-6 and TNFα in response to toll-like receptor stimulation; while cells from the bronchoalveolar lavage (BAL) of ... is known to induce rapid up-regulation of several chemokine receptors on lymphocytes. ...
As a model system, the GPCR-ligand CXCL12 alpha and its receptor CXCR4 are used. Human-derived Ishikawa cells were deposited ... Whether these receptors contribute to the specificity of targeting is less clear. A class of chaperone receptors bearing ... Membrane bound receptors play vital roles in cell signaling, and are the target for many drugs, yet their interactions with ... G-protein-coupled receptors (GPCRs) are prime drug targets and targeted by approximately 60% of current therapeutic drugs such ...
Desensitizes the chemokine receptors CXCR3, CXCR4, and CCR5 (in comparison, NBI-74330 desensitizes only CXCR3) ... Normally, they bind to their respective T cell receptors, activating the T cells and recruiting them to attack the joint ... The T cells in rheumatoid arthritis and other autoimmune diseases express CXCR3, a chemokine receptor associated with cell ... Activates T cell ERK (indicating chemokine receptor signaling and essential for T cell migration), desensitizes CXCR3, and ...
Overexpression of platelet-derived growth factor-BB increases tumor pericyte content via stromal-derived factor-1α/CXCR4 axis. ... Inhibition of vascular smooth muscle G protein-coupled receptor kinase 2 enhances α1D-adrenergic receptor constriction. Am J ... The platelet-derived growth factor receptor-beta phosphorylates and activates G protein-coupled receptor kinase-2. A mechanism ... B and C) Proper signaling of Smads downstream of ALK1 and ALK5 receptor activation depends on GRK2 expression. (B) Grk2+/- ...
Willett, B.J. and Hosie, M.J. (1999) The role of the chemokine receptor CXCR4 in infection with feline immunodeficiency virus. ... Willett, B.J. and Hosie, M.J. (1999) The role of the chemokine receptor CXCR4 in infection with feline immunodeficiency virus. ... 1998) The second extracellular loop of CXCR4 determines its function as a receptor for feline immunodeficiency virus. Journal ... 1998) The second extracellular loop of CXCR4 determines its function as a receptor for feline immunodeficiency virus. Journal ...
Detecting Cell Surface Expression of the G Protein-Coupled Receptor CXCR4.. (Nevins AM, Marchese A.) Methods Mol Biol. 2018; ... Our work is focused primarily on the chemokine receptor CXCR4, a prototypical GPCR implicated in several diseases. Of ... CXCR4 expressing cancer cells tend to disseminate to and colonize anatomical sites where the cognate ligand for CXCR4, called ... Endocytosis is required for CXC chemokine receptor type 4 (CXCR4)-mediated Akt activation and antiapoptotic signaling. ...
  • The CXCL12 chemokine receptor CXCR4 belongs to the GPCR superfamily and is often overexpressed in cancer, being involved in tumor progression and metastasis. (nih.gov)
  • We have investigated in a model system the effect of the EGFR and GRK2 status on CXCL12/CXCR4-mediated activation of Gi, the earliest step downstream of receptor activation. (nih.gov)
  • CXCR-4 is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes. (wikipedia.org)
  • Expression of this receptor in cancer cells has been linked to metastasis to tissues containing a high concentration of CXCL12, such as lungs, liver and bone marrow. (wikipedia.org)
  • However, in breast cancer where SDF1/CXCL12 is also expressed by the cancer cells themselves along with CXCR4, CXCL12 expression is positively correlated with disease free (metastasis free) survival. (wikipedia.org)
  • CXCL12 (over-)expressing cancers might not sense the CXCL12 gradient released from the metastasis target tissues since the receptor, CXCR4, is saturated with the ligand produced in an autocrine manner. (wikipedia.org)
  • Once it is activated by its natural ligand and chemokine, Stromal Cell Derived Factor 1 (SDF-1/CXCL12), the CXCR4 ligand stimulates the stem cells to undergo chemotaxis [4]. (vanderbilt.edu)
  • V160I) in the fourth transmembrane region of CXCR4 was detected in one colon cancer cell line (PD) and one melanoma cell line (LB). CXCR4 was expressed and functional in both PD and LB cells, PD and LB cells migrated specifically toward the receptor ligand, CXCL12 and P-Erk was specifically induced by CXCL12. (cnr.it)
  • In vitro, A431 cells harboring CXCR4(G574A) migrated specifically toward CXCL12 and CXCL12 induced ERK phosphorylation. (cnr.it)
  • Clements D, Markwick LJ, Puri N, Johnson SR. Part from the CXCR4/CXCL12 axis in lymphangioleiomyomatosis and angiomyolipoma. (bioshockinfinitereleasedate.com)
  • The chemokine CXCL12 (stromal cell-derived factor-1, SDF-1) and its receptor CXCR4 play a major role in tumor initiation, promotion, progression and metastasis, especially for breast cancer cells. (cell-signaling-pathways.com)
  • After exposure to CXCL12 or CXCL11, the receptors were rapidly internalized alone or in close proximity. (cell-signaling-pathways.com)
  • This co-internalization was observed either with CXCL11 as the CXCR7-selective ligand (e-h) or with CXCL12 as YIL 781 the ligand for both receptors (i-l). (cell-signaling-pathways.com)
  • As seen best in immunofluorescence, CXCL12 activation initially resulted in a mostly individual internalization of both receptors (5?min, Fig.?2c, place) as detected by individual red and green dots and a lower frequency of yellow (merged fluorescence) dots. (cell-signaling-pathways.com)
  • The human NK cell repertoire is functionally diversified through a tightly regulated differentiation process characterized by an early transition from CD56bright to CD56dim NK cells, followed by coordinated changes in expression of inhibitory receptors, including NKG2A and killer cell immunoglobulin-like receptors (KIR). (confex.com)
  • Weitzenfeld P, Ben-Baruch A. The chemokine program, and its own CCR5 and CXCR4 receptors, as potential goals for individualized therapy in tumor. (bioshockinfinitereleasedate.com)
  • The chemokine receptors CCR5 and CXCR4 belong to the class of 7 transmembrane G-protein-coupled receptors, and their natural ligands are key players in the recruitment of immune cells to sites of inflammation. (medscape.com)
  • CCR5 and CXCR4 are the 2 main co-receptors essential for HIV entry. (medscape.com)
  • Macrophages in chancroid lesions have significantly increased expression of CCR5 and CXCR4 compared with peripheral blood cells, and CD4 T cells have significant up-regulation of CCR5. (medscape.com)
  • Site-directed mutagenesis was used to introduce most of the possible intermediate mutations in the envelope for four distinct coreceptor switch mutants, each with a unique pattern of CCR5 and CXCR4 utilization that extended from highly efficient use of both coreceptors to sole use of CXCR4. (unige.ch)
  • These changes in envelope function were uniform in all four series of envelope mutations and thus were independent of the final use of CCR5 and CXCR4. (unige.ch)
  • Conversely, CXCR4 antagonists may be used to block the metastasis, or spread, of cancer cells by preventing them from moving into other parts of the body. (vanderbilt.edu)
  • Stimulation with the CXCR4- or CXCR7-selective non-peptide antagonists AMD3100 and CCX733 resulted not only in single internalization but partly also in co-internalization of the two receptors. (cell-signaling-pathways.com)
  • Semi-quantification of receptor internalization was achieved by labeling the glycocalyx of the cell surface with WGA (a lectin that binds to sialic acid and phosphorylated Erk, control with antagonists alone). (cell-signaling-pathways.com)
  • d This anti-apoptotic effect could be reversed by co-incubation with the CXCR7-selective antagonist CCX733 (0.1?M) but not significantly by CXCR4-selective antagonist AMD3100 (5?M). Both antagonists experienced no inhibitory effects on their own (not shown). (cell-signaling-pathways.com)
  • CXCR4 antagonists disrupt the specific interaction of chemokines with CXCR4 and may elicit therapeutic potential. (aacrjournals.org)
  • WHIM like mutations in CXCR4 were recently identified in patients with Waldenström's macroglobulinemia, a B-cell malignancy. (wikipedia.org)
  • The presence of CXCR4 WHIM mutations has been associated with clinical resistance to ibrutinib in patients with Waldenström's macroglobulinemia. (wikipedia.org)
  • All patients were MYD88 L265P -mutated, and 17 carried CXCR4 mutations. (nih.gov)
  • CXCR4 mutations did not affect treatment response or progression-free survival. (nih.gov)
  • Because mutations in the CXCR4 gene could regulate its function we sequenced the coding region of the CXCR4 gene in 18 human melanoma and 3 human colon carcinoma cell lines. (cnr.it)
  • Mutations in the CXCR4 gene are found in approximately 30 percent of people with Waldenström macroglobulinemia. (medlineplus.gov)
  • CXCR4 gene mutations involved in Waldenström macroglobulinemia lead to production of an abnormally short CXCR4 protein that cannot be internalized, prolonging signaling activated by the protein. (medlineplus.gov)
  • At least nine mutations in the CXCR4 gene have been found to cause WHIM syndrome, a condition characterized by impaired immune function and recurrent bacterial and viral infections. (medlineplus.gov)
  • As in Waldenström macroglobulinemia, the CXCR4 gene mutations that cause WHIM syndrome impair internalization of the CXCR4 protein. (medlineplus.gov)
  • Recent cancer genome deep sequencing efforts have revealed an unanticipated high frequency of mutations in G proteins and G-protein-coupled receptors (GPCRs) in most tumour types. (nature.com)
  • The syndrome is cause by mutations in CXCR4, a chemokine receptor expressed by hematopoietic and non-hematopoietic cells. (lu.se)
  • In the internalization assay, both SDF-1 and 390 internalized the receptor. (vanderbilt.edu)
  • During this experiment, we conducted two assays: a calcium imaging assay and a receptor internalization assay. (vanderbilt.edu)
  • Also, internalization of the CXCR4 can occur when the receptor is overstimulated or desensitized i.e., during CXCR4 agonist stimulation on CXCR4 expressing cells [9]. (vanderbilt.edu)
  • Therefore, an increase in calcium as well as internalization of CXCR4 was used to confirm that drug 390 was an agonist of the receptor. (vanderbilt.edu)
  • Drugs that block the CXCR4 receptor appear to be capable of "mobilizing" hematopoietic stem cells into the bloodstream as peripheral blood stem cells. (wikipedia.org)
  • The chemotactic function of CXCR4 is demonstrated in the receptor's role of anchoring hematopoietic stem cells in the bone marrow [3]. (vanderbilt.edu)
  • Mutated envelopes with some preservation of entry function on either CCR5- or CXCR4-expressing target cells were further characterized for their sensitivity to CCR5 or CXCR4 inhibitors, soluble CD4, and the neutralizing antibodies b12-IgG and 4E10. (unige.ch)
  • Lymphoma cells are reported to over-express chemokine receptors that favors leukocyte infiltration, promotes tumorigenesis, angiogenesis, immune evasion, and metastasis. (aacrjournals.org)
  • Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. (medlineplus.gov)
  • We demonstrate here that interferon-γ (IFN-γ) increases the expression of chemokine receptors CCR1, CCR3, and CCR5 in monocytoid U937 cells as detected by cell surface molecule labeling and mRNA expression, as well as by intracellular calcium mobilization and cell migration in response to specific ligands. (johnshopkins.edu)
  • A dysregulated immune system (including changes in the number and/or function of immune cells, cytokine levels, and the expression of inhibitory receptors or their ligands) plays a key role in the development of HCC. (wjgnet.com)
  • Moreover, these receptors are functional, as treatment of FRT tissue cells with ligands for TLR and NOD induces production of proinflammatory CXCL8 [ 13 ], and those receptors actively participate in immune response to pathogens, as Neisseria gonorrhea and HIV-1 [ 14 ]. (hindawi.com)
  • Developing computational methods to relate receptors by the similarity of their ligands, rather than by protein sequence or structure. (ucsf.edu)
  • Since the new relationships are articulated by ligands, they may be directly tested both on isolated receptors and, increasingly, against model whole organisms, such as zebra fish, C. elegans and mice. (ucsf.edu)
  • Plerixafor (AMD3100) is a drug, approved for routine clinical use, which directly blocks the CXCR4 receptor. (wikipedia.org)
  • As expected, treatment with AMD3100, a specific CXCR4 inhibitor, reduced the in vivo growth of CXCR4(G574A) tumor b(G574A) but surprisingly, increased the growth of CXCR4(G574A) A431 cells. (cnr.it)
  • While the mutation impairs cell growth in vivo, the CXCR4 inhibitor, AMD3100, stimulated the growth of cells harboring CXCR4(G574A). (cnr.it)
  • These changes were accompanied by increasing resistance to the CXCR4 inhibitor AMD3100. (unige.ch)
  • Chemokine receptor 4 (CXCR4) has been explored with radiolabelled CXCR4 antagonist (AMD3100) for imaging and future targeted radiation therapy for malignant lymphoma. (aacrjournals.org)
  • Until recently, SDF-1 and CXCR4 were believed to be a relatively monogamous ligand-receptor pair (other chemokines are promiscuous, tending to use several different chemokine receptors). (wikipedia.org)
  • As a CXC-type chemokine receptor, or a receptor that responds to CXC chemokines, CXCR4 aids in cell chemotaxis when it is stimulated by chemokines [2]. (vanderbilt.edu)
  • Retinal pigment epithelial (RPE) cells form part of the blood-retina barrier and have recently been shown to produce various chemokines in response to proinflammatory cytokines, As the scope of chemokine action has been shown to extend beyond the regulation of leukocyte migration, we have investigated the expression of chemokine receptors on RPE cells to determine whether they could be a target for chemokine signaling. (elsevierpure.com)
  • In summary, the O'Boyle/Kirby team demonstrated that systemically administered PS372424 engages the chemokine T cell migration system and re-directs chemo-attraction (receptor desensitization) away from inflammatory chemokines expressed in synovial fluid. (jax.org)
  • This process is mediated by chemokines, which guide cell migration by binding to their specific receptors. (confex.com)
  • Chemokines attract the cells that have specific receptors on their surface, and the migration of such cells is aligned with the growth of chemokine concentration. (news-medical.net)
  • The most frequently mutated GPCRs include thyroid-stimulating hormone receptor (TSHR), Smoothened (SMO), glutamate metabotropic receptors (GRMs), members of the adhesion family of GPCRs and receptors for bioactive lipid mediators such as lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) that accumulate in the tumour microenvironment. (nature.com)
  • Aberrant expression and activity of G proteins and G-protein-coupled receptors (GPCRs) are frequently associated with tumorigenesis. (nature.com)
  • We are primarily using cytomegaloviruses to examine how the pathogens alter signaling pathways directed by G-protein coupled receptors (GPCRs) to facilitate robust replication in tissues important for host-host dissemination. (uc.edu)
  • Applying these to G-Protein Coupled Receptors (GPCRs), which are the single largest family of signaling receptors in human cells. (ucsf.edu)
  • 390 may be the first small molecule agonist of CXCR4 receptors ever identified and may have a number of uses in medicine. (vanderbilt.edu)
  • The O'Boyle/Kirby team thwarted the synovium-attacking T cells with PS372424, a small-molecule agonist for CXCR3 and several other chemokine receptors. (jax.org)
  • How CXCR4 signaling integrates with other relevant oncogenic transduction pathways and the role of GPCR regulatory mechanisms in such contexts are not well-understood. (nih.gov)
  • Our data point to a role for GRK2 in the crosstalk of the CXCR4 and EGFR signal transduction pathways in pathological contexts characterized by concurrent overactivation of these proteins. (nih.gov)
  • It is speculated this interaction may be through CXCR4 mediated signalling pathways. (wikipedia.org)
  • After attachment of its ligand, called SDF-1, the CXCR4 protein turns on (activates) signaling pathways inside the cell. (medlineplus.gov)
  • Once signaling is stimulated, the CXCR4 protein is removed from the cell membrane (internalized) and broken down so it can no longer activate the signaling pathways. (medlineplus.gov)
  • Our data provide evidence for a relationship of cellular pathways that are induced by IFN-γ with those that regulate chemokine receptor expression. (johnshopkins.edu)
  • C-X-C chemokine receptor 2 (CXCR2) is a chemotactic receptor that is critical in neutrophil mobilization from bone marrow to blood and tissue sites. (frontiersin.org)
  • In order to delineate the homing patterns of distinct NK cell subsets, we used high-dimensional flow cytometry combined with functional assays to map the NK cell chemokine receptor expression and migratory behavior. (confex.com)
  • Interestingly, CCR1 and CXCR6 were expressed mainly on less differentiated NKG2A+ CD56dim NK cells (B). Next, we stratified the chemokine receptor expression on mature KIR+ NK cells based on the expression of self (educated) or non-self KIR (uneducated). (confex.com)
  • To determine whether the observed differences in chemokine receptor expression translate into altered chemokine responsiveness between the subsets, we combined the transwell system with multicolor flow cytometry. (confex.com)
  • Chemokine receptors (CR), which can mediate migration of immune cells to the site of inflammation, also function as coreceptors for human immunodeficiency virus (HIV) entry into CD4 + T lymphocytes and antigen- presenting cells. (johnshopkins.edu)
  • 186544-26-3 manufacture As in additional tumor entities, CXCR4 overexpression considerably correlates with unfavorable individual outcome. (bioshockinfinitereleasedate.com)
  • As opposed to a great many other tumor entities, the part of CXCR4 manifestation is not evaluated in common and atypical lung carcinoids up to now, and there are just limited data on CXCR4 manifestation in SCLC [26, 27]. (bioshockinfinitereleasedate.com)
  • Furthermore, previous studies looking into the manifestation of CXCR4 in various tumor entities by immunohistochemistry (IHC) frequently yielded just cytoplasmic or nuclear staining of the membrane-bound receptor [28, 29]. (bioshockinfinitereleasedate.com)
  • Hartmann TN, Burger JA, Glodek A, Fujii N, Burger M. CXCR4 chemokine receptor and integrin signaling co-operate in mediating adhesion and chemoresistance in little cell lung tumor (SCLC) cells. (bioshockinfinitereleasedate.com)
  • The function of adhesion substances and chemokine receptor CXCR4 (Compact disc184) in little cell lung tumor. (bioshockinfinitereleasedate.com)
  • Chemokine receptor CXCR4 and early-stage non-small cell lung tumor: design of appearance and relationship with result. (bioshockinfinitereleasedate.com)
  • The CXCR4 receptor on the surface of MSC reacts with the SDF-1 chemokine and makes the cells move closer to the tumor. (news-medical.net)
  • Motixafortide leverages the expression of the CXCR4 receptor on different immune cells and potentiates the immune system against the tumor. (kron4.com)
  • Recent data indicate concurrent upregulation in certain tumors of CXCR4, EGF receptor (EGFR), and G protein-coupled receptor kinase 2 (GRK2), a signaling node functionally linked to both receptor types. (nih.gov)
  • Interestingly, in vivo studies showed that the growth of A431 tumors harboring CXCR4(G574A) was delayed compared to those harboring WT CXCR4. (cnr.it)
  • Introduction For most tumors, the overexpression from the chemokine receptor CXCR4 is connected with increased malignancy and poor individual outcomes. (bioshockinfinitereleasedate.com)
  • We find that overexpressed and activated EGFR reduces CXCR4-mediated Gi1 activation and that GRK2 phosphorylation at tyrosine residues is required to exert its inhibitory actions on CXCR4-Gi stimulation, suggesting a shared path of modulation. (nih.gov)
  • While an agonist activates a receptor, an anatagonist prevents agonist-mediated stimulation of a receptor. (vanderbilt.edu)
  • The level of CXCR4 mRNA expression, but not cell surface expression, increased on stimulation,vith It-lp or TNF-alpha. (elsevierpure.com)
  • The WHIM-like CXCR4(S338X) somatic mutation activates AKT and ERK, and promotes resistance to ibrutinib and other agents used in the treatment of Waldenstrom's Macroglobulinemia. (medlineplus.gov)
  • CXCR4 is one of several chemokine co-receptors that HIV can use to infect CD4+ T cells. (wikipedia.org)
  • It has been also shown that CXCR4 signalling regulates the expression of CD20 on B cells. (wikipedia.org)
  • In a small human clinical trial to evaluate the safety and efficacy of fucoidan ingestion (brown seaweed extract), 3g daily of 75% w/w oral fucoidan for 12 days increased the proportion of CD34+CXCR4+ from 45 to 90% and the serum SDF-1 levels, which could be useful in CD34+ cells homing/mobilization via SDF-1/CXCR4 axis. (wikipedia.org)
  • CXCR4 is the chemokine receptor which aids in chemotaxis of stem cells, such as those in the bone marrow or the brain. (vanderbilt.edu)
  • To determine whether 390 is an agonist to the CXCR4 receptor, we transfected cells with CXCR4 and exposed them to no agonist [vehicle control], SDF-1, or varying concentrations of our agonist drug. (vanderbilt.edu)
  • There was an increase in calcium in the cells when 390 was added, indicating that the receptor was being activated. (vanderbilt.edu)
  • CXCR4 is a chemokine receptor, and is found on a variety cells, including cancerous and stem cells [1]. (vanderbilt.edu)
  • Since these stem cells can be moved in the body through agonist interaction with CXCR4, discovering a small molecule receptor stimulant can potentially facilitate organ or tissue transplants [5]. (vanderbilt.edu)
  • Many types of cancer cells express the CXCR4 receptor and studies have shown that interference with the activation of the receptor by SDF- inhibited the spread of the cancer cells [3]. (vanderbilt.edu)
  • This receptor is also used by the HIV-1 virus to infect human body cells [6]. (vanderbilt.edu)
  • Cell passage using C8161 melanoma cells (passage 17-21) that already have CXCR4 expressed in them were used in the Calcium Imaging Assay. (vanderbilt.edu)
  • To give insight into the function of the mutant CXCR4 receptor, human A431, epidermoid carcinoma cells, were stably transfected with both mutant and wild type CXCR4. (cnr.it)
  • This is the first report of a spontaneously occurring, functionally active CXCR4 mutation in human cancer cells. (cnr.it)
  • The CXCR4 gene provides instructions for making a receptor protein that spans the outer membrane of cells, specifically white blood cells and cells in the brain and spinal cord (central nervous system). (medlineplus.gov)
  • The CXCR4 receptor is also involved in the movement (migration) of cells. (medlineplus.gov)
  • Cells that have the CXCR4 protein in their membrane are attracted to SDF-1. (medlineplus.gov)
  • Researchers suggest that white blood cells that have the CXCR4 protein in their membrane longer than usual are abnormally retained in the bone marrow (a condition known as myelokathexis). (medlineplus.gov)
  • The increased expression of these chemokine receptors also results in an enhanced HIV-1 entry into cells. (johnshopkins.edu)
  • RT-PCR analysis indicated that the predominant receptor expressed on RPE cells was CXCR4. (elsevierpure.com)
  • CXCR4 protein could be detected on the surface of 16% of the RPE cells using flow cytometry, Calcium mobilization in response to the CXCR4 ligand stromal cell-derived factor 1 alpha (SDF-1 alpha) indicated that the CXCR4 receptors were functional, Incubation with SDF-1 alpha resulted in secretion of monocyte chemoattractant protein-1, IL-8, and growth-related oncogene iv, RPE cells also migrated in response to SDF-1 alpha. (elsevierpure.com)
  • As SDF-1 alpha expression by RPE cells was detected constitutively, we postulate that SDP-1-CXCR4 interactions may modulate the affects of chronic inflammation and subretinal neovascularization at the RPE site of the blood-retina barrier. (elsevierpure.com)
  • Immunofluorescence and goldClabeling by light and electron microscopy, respectively, revealed that both receptors were localized at the cell surface in non-stimulated cells. (cell-signaling-pathways.com)
  • Our findings suggest that CXCR4 and CXCR7 closely YIL 781 interact in breast malignancy cells. (cell-signaling-pathways.com)
  • contamination by 4,6-diamidino-2-phenylindole (DAPI) staining and (CXCR4) and (CXCR7) fluorescent (secondary) antibodies in resting cells. (cell-signaling-pathways.com)
  • The T cells in rheumatoid arthritis and other autoimmune diseases express CXCR3, a chemokine receptor associated with cell migration. (jax.org)
  • Normally, they bind to their respective T cell receptors, activating the T cells and recruiting them to attack the joint synovia. (jax.org)
  • Sensitivity to neutralizing antibody was more variable, although infection of CXCR4-expressing targets was generally more sensitive to neutralization by both b12-IgG and 4E10 than infection of CCR5-expressing target cells. (unige.ch)
  • We found that the chemokine-induced migration capability of NK cells correlated closely with the expression level of corresponding chemokine receptor, leading to subset specific responses to various chemokine gradients (D). (confex.com)
  • We demonstrate that targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to CD40 (αCD40.RBD) induces significant levels of specific T and B cells, with long-term memory phenotypes, in a humanized mouse model. (nature.com)
  • The angiogenic effects of IL8 in intestinal microvascular endothelial cells are found to be mediated by this receptor. (cancerindex.org)
  • In this review, we have discussed the status and roles of various immune effector cells ( e.g ., dendritic cells, natural killer cells, macrophages, and T cells), their cytokine profile, and the chemokine-receptor axis in promoting or impeding HCC. (wjgnet.com)
  • Together with the disruption of mucosal and skin barriers, the presence of cells with up-regulated HIV-1 co-receptors in H ducreyi -infected lesions provides an environment that facilitates the acquisition of HIV-1 infection. (medscape.com)
  • Interestingly, receptors which expression declines during NK cell differentiation (CCR5, CCR7, and CXCR3) are commonly associated with adaptive T cell responses to viruses, whereas receptors that are upregulated along the differentiation axis (CXCR1, CXCR2, CX3CR1, CMKLR1) are typical for neutrophils and macrophages as a part of the innate immune response. (confex.com)
  • This receptor also binds to chemokine (C-X-C motif) ligand 1 (CXCL1/MGSA), a protein with melanoma growth stimulating activity, and has been shown to be a major component required for serum-dependent melanoma cell growth. (cancerindex.org)
  • C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the CXCR4 gene. (wikipedia.org)
  • The protein is a CXC chemokine receptor. (wikipedia.org)
  • Dr. Marchese has had a long-standing interest in understanding the molecular mechanisms governing G protein-coupled receptor signaling. (mcw.edu)
  • Research in the Marchese lab is directed towards understanding the molecular mechanisms governing G protein-coupled receptor (GPCR) signaling. (mcw.edu)
  • Human cytomegalovirus G protein-coupled receptor US28 promotes latency by attenuating c-fos. (uc.edu)
  • The protein encoded by this gene is a member of the G-protein-coupled receptor family. (cancerindex.org)
  • This protein is a receptor for interleukin 8 (IL8). (cancerindex.org)
  • Recent evidence demonstrates ubiquitin is also a natural ligand of CXCR4. (wikipedia.org)
  • SDF-1 is the natural ligand for the CXCR4 receptor. (vanderbilt.edu)
  • SDF-1/CXCR4 pair plays a role in the mobilization of CD34 + progenitors to peripheral blood. (biolegend.com)
  • Consequently, the purpose of the present research was the immunohistochemical evaluation of CXCR4 manifestation in BP-NEN using the monoclonal rabbit anti human being CXCR4 antibody UMB-2, which, as opposed to additional anti-CXCR4 antibodies, prospects mainly to membranous staining from the receptor. (bioshockinfinitereleasedate.com)
  • Co-receptor Binding Site Antibodies Enable CD4-Mimetics to Expose Conserved Anti-cluster A ADCC Epitopes on HIV-1 Envelope Glycoproteins. (harvard.edu)
  • This receptor mediates neutrophil migration to sites of inflammation. (cancerindex.org)
  • Knockout studies in mice suggested that this receptor controls the positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. (cancerindex.org)
  • Sex steroid receptors (SSRs), which are involved in BC etiology and progression, promote BCSC proliferation, dedifferentiation and migration. (wjgnet.com)
  • Waldenström macroglobulinemia is thought to result from multiple genetic changes, one of which can be a CXCR4 gene mutation. (medlineplus.gov)
  • This gene, IL8RA, a gene encoding another high affinity IL8 receptor, as well as IL8RBP, a pseudogene of IL8RB, form a gene cluster in a region mapped to chromosome 2q33-q36. (cancerindex.org)
  • The chemokine receptor CXCR4 is widely expressed in human cancers and regulates cell invasion, proliferation and survival. (cnr.it)
  • The SDF-1/CXCR4 pair plays a key role in maintaining proliferation and survival of bone marrow stem cell subpopulations under stress conditions. (biolegend.com)
  • Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. (broadinstitute.org)
  • Motixafortide inhibits CXCR4, a chemokine receptor and a well validated therapeutic target that is over-expressed in many human cancers including pancreatic ductal adenocarcinoma (PDAC). (kron4.com)
  • Human Immunodeficiency Virus Immune Cell Receptors, Coreceptors, and Cofactors: Implications for Prevention and Treatment. (harvard.edu)
  • citation needed] CXCR4 is upregulated during the implantation window in natural and hormone replacement therapy cycles in the endometrium, producing, in presence of a human blastocyst, a surface polarization of the CXCR4 receptors suggesting that this receptor is implicated in the adhesion phase of human implantation. (wikipedia.org)
  • As mentioned earlier, CXCR4 agonists may be crucial in stem cell chemotaxis. (vanderbilt.edu)
  • We have previously reported that a single nucleotide polymorphism (SNP) in leptin receptor (LEPR), present in up to 50% of people, influenced CDI-induced neutrophil CXCR2 expression and tissue neutrophilia. (frontiersin.org)
  • She has also identified immunological correlates of feline retroviral infection, discovered the primary and co-receptor molecules for FIV infection, and more recently identified the first case of human-to-cat transmission of SARS-CoV-2 in the UK. (gla.ac.uk)
  • We studied the evolution of human immunodeficiency virus type 1 (HIV-1) envelope function during the process of coreceptor switching from CCR5 to CXCR4. (unige.ch)
  • HIV being one as HIV is specialised to infect human co-receptor such as CXCR-4 and CCR-5 etc. (bio.net)
  • Cellular receptors that bind the human immunodeficiency virus that causes AIDS. (harvard.edu)
  • Humoral Immune Pressure Selects for HIV-1 CXC-chemokine Receptor 4-using Variants. (harvard.edu)
  • Chronic exposure to THC has been shown to increase T lymphocyte CXCR4 expression on both CD4+ and CD8+ T lymphocytes in rhesus macaques. (wikipedia.org)
  • CXCR4, CCR4, and CCR2 expression was relatively uniform across all subsets. (confex.com)
  • The present results show that peripheral blood NK cell chemokine receptor profile changes in a coordinated fashion during NK cell differentiation and is further influenced by the expression of self-specific KIR. (confex.com)
  • We also showed that bryostatin-1 downregulates the expression of the HIV-1 receptors CD4 and CXCR4 and prevents HIV-1-induced cytotoxicity. (genengnews.com)
  • The results show that the polycation/siRNA/PFOB nanoemulsions are capable of efficiently silencing the expression of STAT3 and inhibiting chemokine receptor CXCR4 - two validated targets in pulmonary fibrosis. (cdc.gov)
  • CXCR4 dimerization is dynamic and increases with concentration. (wikipedia.org)
  • Next, we took calcium images using the dye fura-2, which indicates changes in calcium concentration in the cell due to CXCR4 activation. (vanderbilt.edu)
  • CXCR4 binding efficacy and toxicity studies were performed on CXCR4 expressing cancer cell-lines. (aacrjournals.org)
  • The Phase 2 clinical trial is designed to evaluate the company's CXCR4 inhibitor motixafortide in combination with PD-1 inhibitor cemiplimab and standard of care chemotherapies gemcitabine and nab-paclitaxel, versus gemcitabine and nab-paclitaxel alone, in first-line pancreatic cancer (PDAC). (kron4.com)