A family of G-protein-coupled receptors that was originally identified by its ability to bind N-formyl peptides such as N-FORMYLMETHIONINE LEUCYL-PHENYLALANINE. Since N-formyl peptides are found in MITOCHONDRIA and BACTERIA, this class of receptors is believed to play a role in mediating cellular responses to cellular damage and bacterial invasion. However, non-formylated peptide ligands have also been found for this receptor class.
Cell surface proteins that bind LIPOXINS with high affinity and trigger intracellular changes influencing the behavior of cells.
A formylated tripeptide originally isolated from bacterial filtrates that is positively chemotactic to polymorphonuclear leucocytes, and causes them to release lysosomal enzymes and become metabolically activated.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Cell surface receptors that bind peptide messengers with high affinity and regulate intracellular signals which influence the behavior of cells.
Protein of the annexin family exhibiting lipid interaction and steroid-inducibility.
Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.
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.
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.
Peptides composed of between two and twelve amino acids.
The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cell-surface receptors on the neutrophil.
Trihydroxy derivatives of eicosanoic acids. They are primarily derived from arachidonic acid, however eicosapentaenoic acid derivatives also exist. Many of them are naturally occurring mediators of immune regulation.
Enzymes that catalyze the transfer of hydroxymethyl or formyl groups. EC 2.1.2.
Compounds with a five-membered heterocyclic ring with two nitrogens and a keto OXYGEN. Some are inhibitors of TNF-ALPHA production.
Small cationic peptides that are an important component, in most species, of early innate and induced defenses against invading microbes. In animals they are found on mucosal surfaces, within phagocytic granules, and on the surface of the body. They are also found in insects and plants. Among others, this group includes the DEFENSINS, protegrins, tachyplesins, and thionins. They displace DIVALENT CATIONS from phosphate groups of MEMBRANE LIPIDS leading to disruption of the membrane.
The movement of cells or organisms toward or away from a substance in response to its concentration gradient.
A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.
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)
Antimicrobial cationic peptides with a highly conserved amino terminal cathelin-like domain and a more variable carboxy terminal domain. They are initially synthesized as preproproteins and then cleaved. They are expressed in many tissues of humans and localized to EPITHELIAL CELLS. They kill nonviral pathogens by forming pores in membranes.
A collection of cloned peptides, or chemically synthesized peptides, frequently consisting of all possible combinations of amino acids making up an n-amino acid peptide.
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.
An ACUTE PHASE REACTION protein present in low concentrations in normal sera, but found at higher concentrations in sera of older persons and in patients with AMYLOIDOSIS. It is the circulating precusor of amyloid A protein, which is found deposited in AA type AMYLOID FIBRILS.
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 family of heterotrimeric GTP-binding protein alpha subunits that were originally identified by their ability to inhibit ADENYLYL CYCLASES. Members of this family can couple to beta and gamma G-protein subunits that activate POTASSIUM CHANNELS. The Gi-Go part of the name is also spelled Gi/Go.
Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.
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 that can carry out the process of PHAGOCYTOSIS.
Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.
One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.
Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).
The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.
Disordered formation of various types of leukocytes or an abnormal accumulation or deficiency of these cells.
Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.
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.
Established cell cultures that have the potential to propagate indefinitely.
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)
A set of BACTERIAL ADHESINS and TOXINS, BIOLOGICAL produced by BORDETELLA organisms that determine the pathogenesis of BORDETELLA INFECTIONS, such as WHOOPING COUGH. They include filamentous hemagglutinin; FIMBRIAE PROTEINS; pertactin; PERTUSSIS TOXIN; ADENYLATE CYCLASE TOXIN; dermonecrotic toxin; tracheal cytotoxin; Bordetella LIPOPOLYSACCHARIDES; and tracheal colonization factor.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
The rate dynamics in chemical or physical systems.
Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.
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.
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.
Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids.
A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (GRANULOMATOUS DISEASE, CHRONIC) often die as a result of recurrent bacterial infections.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Tetrahydrofolates which are substituted by a formyl group at either the nitrogen atom in the 5 position or the nitrogen atom in the 10 position. N(5)-Formyltetrahydrofolate is leukovorin (citrovorum factor) while N(10)-formyltetrahydrofolate is an active coenzyme which functions as a carrier of the formyl group in a number of enzymatic reactions.
The process of losing secretory granules (SECRETORY VESICLES). This occurs, for example, in mast cells, basophils, neutrophils, eosinophils, and platelets when secretory products are released from the granules by EXOCYTOSIS.
A PEPTIDE that is secreted by the BRAIN and the HEART ATRIA, stored mainly in cardiac ventricular MYOCARDIUM. It can cause NATRIURESIS; DIURESIS; VASODILATION; and inhibits secretion of RENIN and ALDOSTERONE. It improves heart function. It contains 32 AMINO ACIDS.
A flavoprotein enzyme that catalyzes the univalent reduction of OXYGEN using NADPH as an electron donor to create SUPEROXIDE ANION. The enzyme is dependent on a variety of CYTOCHROMES. Defects in the production of superoxide ions by enzymes such as NADPH oxidase result in GRANULOMATOUS DISEASE, CHRONIC.
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). (From Dictionary of Prostaglandins and Related Compounds, 1990)
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian 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.
Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.
Phenomenon of cell-mediated immunity measured by in vitro inhibition of the migration or phagocytosis of antigen-stimulated LEUKOCYTES or MACROPHAGES. Specific CELL MIGRATION ASSAYS have been developed to estimate levels of migration inhibitory factors, immune reactivity against tumor-associated antigens, and immunosuppressive effects of infectious microorganisms.
Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Derivatives of formic acids. Included under this heading are a broad variety of acid forms, salts, esters, and amides that are formed with a single carbon carboxy group.
A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors (RECEPTORS, VASOACTIVE INTESTINAL PEPTIDE).
Effective in the initiation of protein synthesis. The initiating methionine residue enters the ribosome as N-formylmethionyl tRNA. This process occurs in Escherichia coli and other bacteria as well as in the mitochondria of eucaryotic cells.
Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.
Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.
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.
Peptides that have the ability to enter cells by crossing the plasma membrane directly, or through uptake by the endocytotic pathway.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
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.
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.

Non-serum-dependent chemotactic factors produced by Candida albicans stimulate chemotaxis by binding to the formyl peptide receptor on neutrophils and to an unknown receptor on macrophages. (1/678)

Serum-free culture filtrates of six Candida species and Saccharomyces cerevisiae were found to contain chemoattractants for human polymorphonuclear leukocytes (PMNs) and a mouse macrophage-like cell line, J774. The chemotactic factors differed for the PMN and J774 cells, however, in terms of heat stability, kinetics of liberation by the yeast cells, and divalent cation requirements for production. The chemoattractant in Candida albicans culture filtrates appeared to act through the formyl peptide receptor (FPR) of PMNs, since it was found to induce chemotaxis of Chinese hamster ovary (CHO) cells that were expressing the human FPR but did not induce chemotaxis of wild-type CHO cells. The C. albicans culture filtrates also induced migration of PMNs across confluent monolayers of a human gastrointestinal epithelial cell line, T84; migration occurred in the basolateral-to-apical direction but not the reverse direction, unless the epithelial tight junctions were disrupted. J774 cells did not migrate toward the formylated peptide (fMet-Leu-Phe; fMLF), and chemotaxis toward the C. albicans culture filtrate was not inhibited by an FPR antagonist (t-butoxycarbonyl-Met-Leu-Phe), suggesting that a different receptor mediated J774 cell chemotaxis. In conclusion, we have identified a receptor by which a non-serum-dependent chemotactic factor (NSCF) produced by C. albicans induced chemotaxis of PMNs. Additionally, we have shown that NSCF was active across epithelial monolayers. These findings suggest that NSCFs produced by C. albicans and other yeast species may influence host-pathogen interactions at the gastrointestinal tract mucosal surface by inducing phagocytic-cell infiltration.  (+info)

Yops of Yersinia enterocolitica inhibit receptor-dependent superoxide anion production by human granulocytes. (2/678)

The virulence plasmid-borne genes encoding Yersinia adhesin A (YadA) and several Yersinia secreted proteins (Yops) are involved in the inhibition of phagocytosis and killing of Yersinia enterocolitica by human granulocytes. One of these Yops, YopH, dephosphorylates multiple tyrosine-phosphorylated proteins in eukaryotic cells and is involved in the inhibition of phagocytosis of Y. enterocolitica by human granulocytes. We investigated whether antibody- and complement-opsonized plasmid-bearing (pYV+) Y. enterocolitica inhibits O2- production by human granulocytes in response to various stimuli and whether YopH is involved. Granulocytes were preincubated with mutant strains unable to express YadA or to secrete Yops or YopH. O2- production by granulocytes during stimulation was assessed by measuring the reduction of ferricytochrome c. PYV+ Y. enterocolitica inhibited O2- production by granulocytes incubated with opsonized Y. enterocolitica or N-formyl-Met-Leu-Phe (f-MLP). This inhibitory effect mediated by pYV did not affect receptor-independent O2- production by granulocytes in response to phorbol myristate acetate, indicating that NADPH activity remained unaffected after activation of protein kinase C. The inhibition of f-MLP-induced O2- production by granulocytes depends on the secretion of Yops and not on the expression of YadA. Insertional inactivation of the yopH gene abrogated the inhibition of phagocytosis of antibody- and complement-opsonized Y. enterocolitica by human granulocytes but not of the f-MLP-induced O2- production by granulocytes or tyrosine phosphorylation of granulocyte proteins. These findings suggest that the specific targets for YopH are not present in f-MLP receptor-linked signal transduction and that other Yop-mediated mechanisms are involved.  (+info)

Hmo1p, a high mobility group 1/2 homolog, genetically and physically interacts with the yeast FKBP12 prolyl isomerase. (3/678)

The immunosuppressive drugs FK506 and rapamycin bind to the cellular protein FKBP12, and the resulting FKBP12-drug complexes inhibit signal transduction. FKBP12 is a ubiquitous, highly conserved, abundant enzyme that catalyzes a rate-limiting step in protein folding: peptidyl-prolyl cis-trans isomerization. However, FKBP12 is dispensible for viability in both yeast and mice, and therefore does not play an essential role in protein folding. The functions of FKBP12 may involve interactions with a number of partner proteins, and a few proteins that interact with FKBP12 in the absence of FK506 or rapamycin have been identified, including the ryanodine receptor, aspartokinase, and the type II TGF-beta receptor; however, none of these are conserved from yeast to humans. To identify other targets and functions of FKBP12, we have screened for mutations that are synthetically lethal with an FKBP12 mutation in yeast. We find that mutations in HMO1, which encodes a high mobility group 1/2 homolog, are synthetically lethal with mutations in the yeast FPR1 gene encoding FKBP12. Deltahmo1 and Deltafpr1 mutants share two phenotypes: an increased rate of plasmid loss and slow growth. In addition, Hmo1p and FKBP12 physically interact in FKBP12 affinity chromatography experiments, and two-hybrid experiments suggest that FKBP12 regulates Hmo1p-Hmo1p or Hmo1p-DNA interactions. Because HMG1/2 proteins are conserved from yeast to humans, our findings suggest that FKBP12-HMG1/2 interactions could represent the first conserved function of FKBP12 other than mediating FK506 and rapamycin actions.  (+info)

Modulation of formyl peptide receptor expression by IL-10 in human monocytes and neutrophils. (4/678)

IL-10, originally described as a cytokine synthesis inhibitory factor, is secreted by a number of cells of the immune system, including monocytes and T cells. Although IL-10 is being assigned as an immunosuppressive cytokine, our study showed that FMLP-R mRNA was rapidly up-regulated by exposure of monocytes to graded concentrations of this cytokine, with maximal (three- to fourfold) stimulation with 10 ng/ml. The effect was rapid, being observable as early as 1 h of treatment with IL-10, maximal between 2 and 4 h, and still evident after 24 h and was associated with an increase of receptor expression on the cell surface as assessed by flow cytometry analysis. Pretreatment of monocytes with actinomycin D completely abrogated the effect of IL-10, suggesting a transcriptional regulation. Moreover, IL-10-treated monocytes showed a significantly enhanced functional responsiveness to FMLP with enhanced (three- to fourfold) chemotaxis and augmented (twofold) intracellular calcium mobilization. In polymorphonuclear neutrophils (PMN), IL-10 also mediated a twofold augmentation of FMLP-R expression. In parallel experiments, we observed that IL-10 could differentially modulate other chemotactic receptors. Hence, we observed that IL-10 augmented two-to threefold platelet-activating factor receptor (PAF-R) expression, whereas it had no significant effect on the fifth component of complement (C5a) receptor (C5a-R) expression. Collectively, our results demonstrate that IL-10 may play an important role in inflammatory process through modulation of chemotactic receptor expression.  (+info)

Dynamics of a chemoattractant receptor in living neutrophils during chemotaxis. (5/678)

Persistent directional movement of neutrophils in shallow chemotactic gradients raises the possibility that cells can increase their sensitivity to the chemotactic signal at the front, relative to the back. Redistribution of chemoattractant receptors to the anterior pole of a polarized neutrophil could impose asymmetric sensitivity by increasing the relative strength of detected signals at the cell's leading edge. Previous experiments have produced contradictory observations with respect to receptor location in moving neutrophils. To visualize a chemoattractant receptor directly during chemotaxis, we expressed a green fluorescent protein (GFP)-tagged receptor for a complement component, C5a, in a leukemia cell line, PLB-985. Differentiated PLB-985 cells, like neutrophils, adhere, spread, and polarize in response to a uniform concentration of chemoattractant, and orient and crawl toward a micropipette containing chemoattractant. Recorded in living cells, fluorescence of the tagged receptor, C5aR-GFP, shows no apparent increase anywhere on the plasma membrane of polarized and moving cells, even at the leading edge. During chemotaxis, however, some cells do exhibit increased amounts of highly folded plasma membrane at the leading edge, as detected by a fluorescent probe for membrane lipids; this is accompanied by an apparent increase of C5aR-GFP fluorescence, which is directly proportional to the accumulation of plasma membrane. Thus neutrophils do not actively concentrate chemoattractant receptors at the leading edge during chemotaxis, although asymmetrical distribution of membrane may enrich receptor number, relative to adjacent cytoplasmic volume, at the anterior pole of some polarized cells. This enrichment could help to maintain persistent migration in a shallow gradient of chemoattractant.  (+info)

Lipopolysaccharide-coated erythrocytes activate human neutrophils via CD14 while subsequent binding is through CD11b/CD18. (6/678)

Interaction of LPS with monocytes and neutrophils is known to occur via CD14 and is strongly enhanced by LPS-binding protein (LBP). Integrins as well as CD14 play a role in the interaction of erythrocytes (E) coated with LPS or whole Gram-negative bacteria with phagocytes. We reasoned that the density of LPS on a particle is an important determinant in these interactions. Therefore, E were coated with different concentrations of LPS (ELPS). The binding of these ELPS to neutrophils was evaluated by flow cytometry. Simultaneously, we measured fMLP receptor expression to evaluate neutrophil activation. ELPS only bound to neutrophils in the presence of LBP. Blocking CD14 inhibited both activation and binding, whereas blocking complement (C) receptor 3 (CR3) inhibited binding but not activation. TNF activation restored ELPS binding in CD14-blocked cells but not in cells in which CR3 was blocked. Salmonella minnesota did bind to neutrophils independent of CR3 or CD14. The addition of LBP enhanced binding twofold, and this surplus was dependent upon CD14 but not on CR3. We conclude that ELPS interact with neutrophils via CD14, initially giving rise to cell activation; subsequently, binding is solely mediated by activated CR3.  (+info)

Does formyl-methionyl-leucyl-phenylalanine exert a physiological role in labor in women? (7/678)

The classical chemotactic receptor for N-formyl peptides has traditionally been associated with polymorphonuclear and mononuclear phagocytes; however, several recent reports indicate that this receptor is also expressed in non-myeloid cells. In this study we have investigated the presence of binding sites for formyl-methionyl-leucyl-phenylalanine (fMLP) in human amniotic membranes of laboring and nonlaboring women; we have also evaluated the effect of the peptide on prostaglandin E (PGE) release from the same tissue. Our results demonstrate the presence of specific, saturable binding sites for 3H-fMLP; Scatchard plot analysis suggests the presence of both high- and low-affinity binding sites in laboring amnion, while only the low-affinity receptors were evident in nonlaboring tissue. N-t-butoxycarbonyl-methionyl-leucyl-phenylalanine (Boc-MLP), a formyl peptide receptor antagonist, inhibited 3H-fMLP binding in both preparations. In addition, fMLP was able to significantly increase PGE synthesis in perifused amnion fragments from laboring and nonlaboring women. This effect was counteracted by Boc-MLP treatment. The presence of specific binding sites for fMLP in amniotic tissue and their differing expression in laboring versus nonlaboring membranes, together with the action of the peptide on PGE synthesis, all suggest a physiological role for fMLP in labor.  (+info)

T21/DP107, A synthetic leucine zipper-like domain of the HIV-1 envelope gp41, attracts and activates human phagocytes by using G-protein-coupled formyl peptide receptors. (8/678)

A leucine zipper-like domain, T21/DP107, located in the amino terminus of the ectodomain of gp41, is crucial to the formation of fusogenic configuration of the HIV-1 envelope protein gp41. We report that the synthetic T21/DP107 segment is a potent stimulant of migration and calcium mobilization in human monocytes and neutrophils. The activity of T21/DP107 on phagocytes was pertussis toxin-sensitive, suggesting this peptide uses Gi-coupled seven-transmembrane receptor(s). Since the bacterial chemotactic peptide fMLP partially desensitized the calcium-mobilizing activity of T21/DP107 in phagocytes, we postulated that T21/DP107 might preferentially use a lower affinity fMLP receptor. By using cells transfected to express cloned prototype chemotactic N-formyl peptide receptor (FPR) or its variant, FPR-like 1 (FPRL1), we demonstrate that T21/DP107 activates both receptors but has a much higher efficacy for FPRL1. In addition, T21/DP107 at nM concentrations induced migration of FPRL1-transfected human embryonic kidney 293 cells. In contrast, fMLP did not induce significant chemotaxis of the same cells at a concentration as high as 50 microM. Although a lipid metabolite, lipoxin A4, was a high-affinity ligand for FPRL1, it was not reported to induce Ca2+ mobilization or chemotaxis in FPRL1-transfected cells. Therefore, T21/DP107 is a first chemotactic peptide agonist identified thus far for FPRL1. Our results suggest that this peptide domain of the HIV-1 gp41 may have the potential to activate host innate immune response by interacting with FPR and FPRL1 on phagocytes.  (+info)

Formyl peptide receptors (FPRs) are a type of G protein-coupled receptors that play a crucial role in the innate immune system. They are expressed on various cells including neutrophils, monocytes, and macrophages. FPRs recognize and respond to formylated peptides derived from bacteria, mitochondria, and host proteins during cell damage or stress. Activation of FPRs triggers a variety of cellular responses, such as chemotaxis, phagocytosis, and release of inflammatory mediators, which help to eliminate invading pathogens and promote tissue repair. There are three subtypes of human FPRs (FPR1, FPR2, and FPR3) that have distinct ligand specificities and functions in the immune response.

Lipoxins are a group of anti-inflammatory mediators that play a role in the resolution of inflammation. They are produced from arachidonic acid, a type of omega-6 fatty acid, through the action of lipoxygenase enzymes. There are several types of lipoxin receptors (ALX/FPR2 and GPR31) that have been identified, which belong to the family of G protein-coupled receptors. These receptors are expressed in various tissues, including the cardiovascular, respiratory, and gastrointestinal systems. Activation of lipoxin receptors leads to a variety of cellular responses, such as inhibition of inflammatory cytokine production, reduction of oxidative stress, and promotion of tissue repair. Dysregulation of the lipoxin signaling pathway has been implicated in several diseases, including asthma, atherosclerosis, and cancer.

N-Formylmethionine Leucyl-Phenylalanine (fMLP) is not a medical condition, but rather a synthetic peptide that is often used in laboratory settings for research purposes. It is a formylated methionine residue linked to a leucine and phenylalanine tripeptide.

fMLP is a potent chemoattractant for certain types of white blood cells, including neutrophils and monocytes. When these cells encounter fMLP, they are stimulated to migrate towards the source of the peptide and release various inflammatory mediators. As such, fMLP is often used in studies of inflammation, immune cell function, and signal transduction pathways.

It's important to note that while fMLP has important research applications, it is not a substance that would be encountered or used in clinical medicine.

Peptides are short chains of amino acid residues linked by covalent bonds, known as peptide bonds. They are formed when two or more amino acids are joined together through a condensation reaction, which results in the elimination of a water molecule and the formation of an amide bond between the carboxyl group of one amino acid and the amino group of another.

Peptides can vary in length from two to about fifty amino acids, and they are often classified based on their size. For example, dipeptides contain two amino acids, tripeptides contain three, and so on. Oligopeptides typically contain up to ten amino acids, while polypeptides can contain dozens or even hundreds of amino acids.

Peptides play many important roles in the body, including serving as hormones, neurotransmitters, enzymes, and antibiotics. They are also used in medical research and therapeutic applications, such as drug delivery and tissue engineering.

Peptide receptors are a type of cell surface receptor that bind to peptide hormones and neurotransmitters. These receptors play crucial roles in various physiological processes, including regulation of appetite, pain perception, immune function, and cardiovascular homeostasis. Peptide receptors belong to the G protein-coupled receptor (GPCR) superfamily or the tyrosine kinase receptor family. Upon binding of a peptide ligand, these receptors activate intracellular signaling cascades that ultimately lead to changes in cell behavior and communication with other cells.

Peptide receptors can be classified into two main categories: metabotropic and ionotropic. Metabotropic peptide receptors are GPCRs, which activate intracellular signaling pathways through coupling with heterotrimeric G proteins. These receptors typically have seven transmembrane domains and undergo conformational changes upon ligand binding, leading to the activation of downstream effectors such as adenylyl cyclase, phospholipase C, or ion channels.

Ionotropic peptide receptors are ligand-gated ion channels that directly modulate ion fluxes across the cell membrane upon ligand binding. These receptors contain four or five subunits arranged around a central pore and undergo conformational changes to allow ion flow through the channel.

Examples of peptide receptors include:

1. Opioid receptors (μ, δ, κ) - bind endogenous opioid peptides such as enkephalins, endorphins, and dynorphins to modulate pain perception and reward processing.
2. Somatostatin receptors (SSTR1-5) - bind somatostatin and cortistatin to regulate hormone secretion, cell proliferation, and angiogenesis.
3. Neuropeptide Y receptors (Y1-Y5) - bind neuropeptide Y to modulate feeding behavior, energy metabolism, and cardiovascular function.
4. Calcitonin gene-related peptide receptor (CGRP-R) - binds calcitonin gene-related peptide to mediate vasodilation and neurogenic inflammation.
5. Bradykinin B2 receptor (B2R) - binds bradykinin to induce pain, inflammation, and vasodilation.
6. Vasoactive intestinal polypeptide receptors (VPAC1, VPAC2) - bind vasoactive intestinal peptide to regulate neurotransmission, hormone secretion, and smooth muscle contraction.
7. Oxytocin receptor (OXTR) - binds oxytocin to mediate social bonding, maternal behavior, and uterine contractions during childbirth.
8. Angiotensin II type 1 receptor (AT1R) - binds angiotensin II to regulate blood pressure, fluid balance, and cell growth.

Annexin A1 is a protein that belongs to the annexin family, which are calcium-dependent phospholipid-binding proteins. This protein is found in various tissues, including the human body, and has multiple functions, such as anti-inflammatory, anti-proliferative, and pro-resolving activities. It plays a crucial role in regulating cellular processes like apoptosis (programmed cell death), membrane organization, and signal transduction.

Annexin A1 is also known to interact with other proteins and receptors, such as the formyl peptide receptor 2 (FPR2), which contributes to its immunomodulatory functions. In addition, it has been implicated in several pathophysiological conditions, including cancer, inflammation, and autoimmune diseases.

Modulating Annexin A1 levels or activity may provide therapeutic benefits for various medical conditions; however, further research is required to fully understand its potential as a drug target.

Immunologic receptors are specialized proteins found on the surface of immune cells that recognize and bind to specific molecules, known as antigens, on the surface of pathogens or infected cells. This binding triggers a series of intracellular signaling events that activate the immune cell and initiate an immune response.

There are several types of immunologic receptors, including:

1. T-cell receptors (TCRs): These receptors are found on the surface of T cells and recognize antigens presented in the context of major histocompatibility complex (MHC) molecules.
2. B-cell receptors (BCRs): These receptors are found on the surface of B cells and recognize free antigens in solution.
3. Pattern recognition receptors (PRRs): These receptors are found inside immune cells and recognize conserved molecular patterns associated with pathogens, such as lipopolysaccharides and flagellin.
4. Fc receptors: These receptors are found on the surface of various immune cells and bind to the constant region of antibodies, mediating effector functions such as phagocytosis and antibody-dependent cellular cytotoxicity (ADCC).

Immunologic receptors play a critical role in the recognition and elimination of pathogens and infected cells, and dysregulation of these receptors can lead to immune disorders and diseases.

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.

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.

Oligopeptides are defined in medicine and biochemistry as short chains of amino acids, typically containing fewer than 20 amino acid residues. These small peptides are important components in various biological processes, such as serving as signaling molecules, enzyme inhibitors, or structural elements in some proteins. They can be found naturally in foods and may also be synthesized for use in medical research and therapeutic applications.

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.

A peptide fragment is a short chain of amino acids that is derived from a larger peptide or protein through various biological or chemical processes. These fragments can result from the natural breakdown of proteins in the body during regular physiological processes, such as digestion, or they can be produced experimentally in a laboratory setting for research or therapeutic purposes.

Peptide fragments are often used in research to map the structure and function of larger peptides and proteins, as well as to study their interactions with other molecules. In some cases, peptide fragments may also have biological activity of their own and can be developed into drugs or diagnostic tools. For example, certain peptide fragments derived from hormones or neurotransmitters may bind to receptors in the body and mimic or block the effects of the full-length molecule.

Neutrophil activation refers to the process by which neutrophils, a type of white blood cell, become activated in response to a signal or stimulus, such as an infection or inflammation. This activation triggers a series of responses within the neutrophil that enable it to carry out its immune functions, including:

1. Degranulation: The release of granules containing enzymes and other proteins that can destroy microbes.
2. Phagocytosis: The engulfment and destruction of microbes through the use of reactive oxygen species (ROS) and other toxic substances.
3. Formation of neutrophil extracellular traps (NETs): A process in which neutrophils release DNA and proteins to trap and kill microbes outside the cell.
4. Release of cytokines and chemokines: Signaling molecules that recruit other immune cells to the site of infection or inflammation.

Neutrophil activation is a critical component of the innate immune response, but excessive or uncontrolled activation can contribute to tissue damage and chronic inflammation.

Lipoxins are a group of naturally occurring, short-lived signaling molecules called eicosanoids that are derived from arachidonic acid, a type of omega-6 fatty acid. They were first discovered in the 1980s and are produced by cells involved in the inflammatory response, such as white blood cells (leukocytes).

Lipoxins have potent anti-inflammatory effects and play a crucial role in regulating and resolving the inflammatory response. They work by modulating the activity of various immune cells, including neutrophils, monocytes, and lymphocytes, and promoting the resolution of inflammation through the activation of anti-inflammatory pathways.

Lipoxins have been shown to have potential therapeutic applications in a variety of inflammatory diseases, such as asthma, arthritis, and inflammatory bowel disease. However, further research is needed to fully understand their mechanisms of action and therapeutic potential.

Hydroxymethyl and Formyl Transferases are a class of enzymes that catalyze the transfer of hydroxymethyl or formyl groups from one molecule to another. These enzymes play important roles in various metabolic pathways, including the synthesis and modification of nucleotides, amino acids, and other biomolecules.

One example of a Hydroxymethyl Transferase is DNA methyltransferase (DNMT), which catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to the 5-carbon of cytosine residues in DNA, forming 5-methylcytosine. This enzyme can also function as a Hydroxymethyl Transferase by catalyzing the transfer of a hydroxymethyl group from SAM to cytosine residues, forming 5-hydroxymethylcytosine.

Formyl Transferases are another class of enzymes that catalyze the transfer of formyl groups from one molecule to another. One example is formyltransferase domain containing protein 1 (FTCD1), which catalyzes the transfer of a formyl group from 10-formyltetrahydrofolate to methionine, forming N5-formiminotetrahydrofolate and methionine semialdehyde.

These enzymes are essential for maintaining proper cellular function and are involved in various physiological processes, including gene regulation, DNA repair, and metabolism. Dysregulation of these enzymes has been implicated in several diseases, including cancer, neurological disorders, and cardiovascular disease.

Pyrazolones are a group of non-steroidal anti-inflammatory drugs (NSAIDs) that contain a pyrazole ring in their chemical structure. They have analgesic, antipyretic, and anti-inflammatory properties. Pyrazolones include drugs such as phenylbutazone, oxyphenbutazone, and aminopyrine. However, due to their potential for serious side effects, including agranulocytosis (a severe decrease in white blood cells), pyrazolones are rarely used in modern clinical practice.

Antimicrobial cationic peptides (ACPs) are a group of small, naturally occurring peptides that possess broad-spectrum antimicrobial activity against various microorganisms, including bacteria, fungi, viruses, and parasites. They are called "cationic" because they contain positively charged amino acid residues (such as lysine and arginine), which allow them to interact with and disrupt the negatively charged membranes of microbial cells.

ACPs are produced by a wide range of organisms, including humans, animals, and plants, as part of their innate immune response to infection. They play an important role in protecting the host from invading pathogens by directly killing them or inhibiting their growth.

The antimicrobial activity of ACPs is thought to be mediated by their ability to disrupt the membranes of microbial cells, leading to leakage of cellular contents and death. Some ACPs may also have intracellular targets, such as DNA or protein synthesis, that contribute to their antimicrobial activity.

ACPs are being studied for their potential use as therapeutic agents to treat infectious diseases, particularly those caused by drug-resistant bacteria. However, their clinical application is still in the early stages of development due to concerns about their potential toxicity to host cells and the emergence of resistance mechanisms in microbial pathogens.

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.

The term "Receptor, Anaphylatoxin C5a" refers to a specific type of receptor found on the surface of various cells in the human body, including immune cells and endothelial cells. This receptor binds to a molecule called C5a, which is a cleavage product of the complement component C5 and is one of the most potent anaphylatoxins.

Anaphylatoxins are inflammatory mediators that play a crucial role in the immune response, particularly in the activation of the complement system and the recruitment of immune cells to sites of infection or injury. C5a is generated during the activation of the complement system and has a wide range of biological activities, including chemotaxis (attracting immune cells to the site of inflammation), increased vascular permeability, and the activation of immune cells such as neutrophils, monocytes, and mast cells.

The C5a receptor, also known as CD88, is a G protein-coupled receptor that belongs to the superfamily of seven transmembrane domain receptors. When C5a binds to the receptor, it triggers a series of intracellular signaling events that lead to the activation of various cellular responses, such as the release of inflammatory mediators and the recruitment of immune cells to the site of inflammation.

Abnormal activation of the C5a/C5a receptor pathway has been implicated in a variety of inflammatory diseases, including sepsis, acute respiratory distress syndrome (ARDS), and autoimmune disorders. Therefore, targeting this pathway with therapeutic agents has emerged as a promising strategy for the treatment of these conditions.

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.

Cathelicidins are a family of antimicrobial peptides that are widely distributed in nature and play an important role in the innate immune system. They are expressed in various tissues, including the epithelia of the respiratory, gastrointestinal, and urogenital tracts, as well as in immune cells such as neutrophils and macrophages.

The human cathelicidin gene is called CAMP (camp gene) and encodes a precursor protein called hCAP-18 (human cationic antimicrobial protein of 18 kDa). After cleavage by proteolytic enzymes, the active peptide LL-37 is generated.

LL-37 has broad-spectrum antimicrobial activity against bacteria, viruses, fungi, and parasites. It also has immunomodulatory functions, such as chemotaxis of immune cells, modulation of cytokine production, and promotion of wound healing. Dysregulation of cathelicidins has been implicated in various inflammatory diseases, including chronic obstructive pulmonary disease (COPD), psoriasis, and rosacea.

A peptide library is a collection of a large number of peptides, which are short chains of amino acids. Each peptide in the library is typically composed of a defined length and sequence, and may contain a variety of different amino acids. Peptide libraries can be synthesized using automated techniques and are often used in scientific research to identify potential ligands (molecules that bind to specific targets) or to study the interactions between peptides and other molecules.

In a peptide library, each peptide is usually attached to a solid support, such as a resin bead, and the entire library can be created using split-and-pool synthesis techniques. This allows for the rapid and efficient synthesis of a large number of unique peptides, which can then be screened for specific activities or properties.

Peptide libraries are used in various fields such as drug discovery, proteomics, and molecular biology to identify potential therapeutic targets, understand protein-protein interactions, and develop new diagnostic tools.

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.

Serum Amyloid A (SAA) protein is an acute phase protein produced primarily in the liver, although it can also be produced by other cells in response to inflammation. It is a member of the apolipoprotein family and is found in high-density lipoproteins (HDL) in the blood. SAA protein levels increase rapidly during the acute phase response to infection, trauma, or tissue damage, making it a useful biomarker for inflammation.

In addition to its role as an acute phase protein, SAA has been implicated in several disease processes, including atherosclerosis and amyloidosis. In amyloidosis, SAA can form insoluble fibrils that deposit in various tissues, leading to organ dysfunction. There are four subtypes of SAA in humans (SAA1, SAA2, SAA3, and SAA4), with SAA1 and SAA2 being the most responsive to inflammatory stimuli.

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.

GTP-binding protein alpha subunits, Gi-Go, are a type of heterotrimeric G proteins that play a crucial role in signal transduction pathways associated with many hormones and neurotransmitters. These G proteins are composed of three subunits: alpha, beta, and gamma. The "Gi-Go" specifically refers to the alpha subunit of these G proteins, which can exist in two isoforms, Gi and Go.

When a G protein-coupled receptor (GPCR) is activated by an agonist, it undergoes a conformational change that allows it to act as a guanine nucleotide exchange factor (GEF). The GEF activity of the GPCR promotes the exchange of GDP for GTP on the alpha subunit of the heterotrimeric G protein. Once GTP is bound, the alpha subunit dissociates from the beta-gamma dimer and can then interact with downstream effectors to modulate various cellular responses.

The Gi-Go alpha subunits are inhibitory in nature, meaning that they typically inhibit the activity of adenylyl cyclase, an enzyme responsible for converting ATP to cAMP. This reduction in cAMP levels can have downstream effects on various cellular processes, such as gene transcription, ion channel regulation, and metabolic pathways.

In summary, GTP-binding protein alpha subunits, Gi-Go, are heterotrimeric G proteins that play an essential role in signal transduction pathways by modulating adenylyl cyclase activity upon GPCR activation, ultimately influencing various cellular responses through cAMP regulation.

GTP-binding proteins, also known as G proteins, are a family of molecular switches present in many organisms, including humans. They play a crucial role in signal transduction pathways, particularly those involved in cellular responses to external stimuli such as hormones, neurotransmitters, and sensory signals like light and odorants.

G proteins are composed of three subunits: α, β, and γ. The α-subunit binds GTP (guanosine triphosphate) and acts as the active component of the complex. When a G protein-coupled receptor (GPCR) is activated by an external signal, it triggers a conformational change in the associated G protein, allowing the α-subunit to exchange GDP (guanosine diphosphate) for GTP. This activation leads to dissociation of the G protein complex into the GTP-bound α-subunit and the βγ-subunit pair. Both the α-GTP and βγ subunits can then interact with downstream effectors, such as enzymes or ion channels, to propagate and amplify the signal within the cell.

The intrinsic GTPase activity of the α-subunit eventually hydrolyzes the bound GTP to GDP, which leads to re-association of the α and βγ subunits and termination of the signal. This cycle of activation and inactivation makes G proteins versatile signaling elements that can respond quickly and precisely to changing environmental conditions.

Defects in G protein-mediated signaling pathways have been implicated in various diseases, including cancer, neurological disorders, and cardiovascular diseases. Therefore, understanding the function and regulation of GTP-binding proteins is essential for developing targeted therapeutic strategies.

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.

Phagocytes are a type of white blood cell in the immune system that engulf and destroy foreign particles, microbes, and cellular debris. They play a crucial role in the body's defense against infection and tissue damage. There are several types of phagocytes, including neutrophils, monocytes, macrophages, and dendritic cells. These cells have receptors that recognize and bind to specific molecules on the surface of foreign particles or microbes, allowing them to engulf and digest the invaders. Phagocytosis is an important mechanism for maintaining tissue homeostasis and preventing the spread of infection.

Superoxides are partially reduced derivatives of oxygen that contain one extra electron, giving them an overall charge of -1. They are highly reactive and unstable, with the most common superoxide being the hydroxyl radical (•OH-) and the superoxide anion (O2-). Superoxides are produced naturally in the body during metabolic processes, particularly within the mitochondria during cellular respiration. They play a role in various physiological processes, but when produced in excess or not properly neutralized, they can contribute to oxidative stress and damage to cells and tissues, potentially leading to the development of various diseases such as cancer, atherosclerosis, and neurodegenerative disorders.

Pertussis toxin is an exotoxin produced by the bacterium Bordetella pertussis, which is responsible for causing whooping cough in humans. This toxin has several effects on the host organism, including:

1. Adenylyl cyclase activation: Pertussis toxin enters the host cell and modifies a specific G protein (Gαi), leading to the continuous activation of adenylyl cyclase. This results in increased levels of intracellular cAMP, which disrupts various cellular processes.
2. Inhibition of immune response: Pertussis toxin impairs the host's immune response by inhibiting the migration and function of immune cells like neutrophils and macrophages. It also interferes with antigen presentation and T-cell activation, making it difficult for the body to clear the infection.
3. Increased inflammation: The continuous activation of adenylyl cyclase by pertussis toxin leads to increased production of proinflammatory cytokines, contributing to the severe coughing fits and other symptoms associated with whooping cough.

Pertussis toxin is an essential virulence factor for Bordetella pertussis, and its effects contribute significantly to the pathogenesis of whooping cough. Vaccination against pertussis includes inactivated or genetically detoxified forms of pertussis toxin, which provide immunity without causing disease symptoms.

Cyclic peptides are a type of peptides in which the N-terminus and C-terminus of the peptide chain are linked to form a circular structure. This is in contrast to linear peptides, which have a straight peptide backbone with a free N-terminus and C-terminus. The cyclization of peptides can occur through various mechanisms, including the formation of an amide bond between the N-terminal amino group and the C-terminal carboxylic acid group (head-to-tail cyclization), or through the formation of a bond between side chain functional groups.

Cyclic peptides have unique structural and chemical properties that make them valuable in medical and therapeutic applications. For example, they are more resistant to degradation by enzymes compared to linear peptides, which can increase their stability and half-life in the body. Additionally, the cyclic structure allows for greater conformational rigidity, which can enhance their binding affinity and specificity to target molecules.

Cyclic peptides have been explored as potential therapeutics for a variety of diseases, including cancer, infectious diseases, and neurological disorders. They have also been used as tools in basic research to study protein-protein interactions and cell signaling pathways.

Complement C5a is a protein fragment that is generated during the activation of the complement system, which is a part of the immune system. The complement system helps to eliminate pathogens and damaged cells from the body by tagging them for destruction and attracting immune cells to the site of infection or injury.

C5a is formed when the fifth component of the complement system (C5) is cleaved into two smaller fragments, C5a and C5b, during the complement activation cascade. C5a is a potent pro-inflammatory mediator that can attract and activate various immune cells, such as neutrophils, monocytes, and eosinophils, to the site of infection or injury. It can also increase vascular permeability, promote the release of histamine, and induce the production of reactive oxygen species, all of which contribute to the inflammatory response.

However, excessive or uncontrolled activation of the complement system and generation of C5a can lead to tissue damage and inflammation, contributing to the pathogenesis of various diseases, such as sepsis, acute respiratory distress syndrome (ARDS), and autoimmune disorders. Therefore, targeting C5a or its receptors has been explored as a potential therapeutic strategy for these conditions.

Leukocyte disorders, also known as white blood cell disorders, refer to a group of conditions that affect the production, function, or number of leukocytes (white blood cells) in the body. Leukocytes play a crucial role in protecting the body against infection and disease. Therefore, disorders that affect these cells can significantly impact an individual's immune system and overall health.

There are several types of leukocyte disorders, including:

1. Leukopenia: A condition characterized by abnormally low levels of white blood cells in the blood. This can increase the risk of infection.
2. Leukocytosis: A condition characterized by an elevated number of white blood cells in the blood. While this can be a normal response to infection or inflammation, it can also indicate an underlying medical condition such as leukemia.
3. Neutropenia: A condition characterized by abnormally low levels of neutrophils, a type of white blood cell that helps fight bacterial infections. This can increase the risk of infection.
4. Neutrophilia: A condition characterized by an elevated number of neutrophils in the blood. This can be a normal response to infection or inflammation, but it can also indicate an underlying medical condition such as an acute bacterial infection.
5. Lymphocytosis: A condition characterized by an elevated number of lymphocytes, a type of white blood cell that helps fight viral infections and cancer cells. This can be a normal response to infection or vaccination, but it can also indicate an underlying medical condition such as chronic lymphocytic leukemia.
6. Lymphopenia: A condition characterized by abnormally low levels of lymphocytes in the blood. This can increase the risk of infection and indicate an underlying medical condition such as HIV/AIDS or autoimmune disorders.
7. Monocytosis: A condition characterized by an elevated number of monocytes, a type of white blood cell that helps fight chronic infections and cancer cells. This can be a normal response to infection or inflammation, but it can also indicate an underlying medical condition such as chronic inflammatory diseases.
8. Monocytopenia: A condition characterized by abnormally low levels of monocytes in the blood. This can increase the risk of infection and indicate an underlying medical condition such as bone marrow disorders or autoimmune diseases.

These conditions can be caused by various factors, including infections, inflammation, cancer, autoimmune disorders, medications, and genetic disorders. Proper diagnosis and treatment require a thorough evaluation of the patient's medical history, physical examination, laboratory tests, and imaging 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.

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.

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.

Virulence factors in Bordetella pertussis, the bacterium that causes whooping cough, refer to the characteristics or components of the organism that contribute to its ability to cause disease. These virulence factors include:

1. Pertussis Toxin (PT): A protein exotoxin that inhibits the immune response and affects the nervous system, leading to the characteristic paroxysmal cough of whooping cough.
2. Adenylate Cyclase Toxin (ACT): A toxin that increases the levels of cAMP in host cells, disrupting their function and contributing to the pathogenesis of the disease.
3. Filamentous Hemagglutinin (FHA): A surface protein that allows the bacterium to adhere to host cells and evade the immune response.
4. Fimbriae: Hair-like appendages on the surface of the bacterium that facilitate adherence to host cells.
5. Pertactin (PRN): A surface protein that also contributes to adherence and is a common component of acellular pertussis vaccines.
6. Dermonecrotic Toxin: A toxin that causes localized tissue damage and necrosis, contributing to the inflammation and symptoms of whooping cough.
7. Tracheal Cytotoxin: A toxin that damages ciliated epithelial cells in the respiratory tract, impairing mucociliary clearance and increasing susceptibility to infection.

These virulence factors work together to enable Bordetella pertussis to colonize the respiratory tract, evade the host immune response, and cause the symptoms of whooping cough.

Monocytes are a type of white blood cell that are part of the immune system. They are large cells with a round or oval shape and a nucleus that is typically indented or horseshoe-shaped. Monocytes are produced in the bone marrow and then circulate in the bloodstream, where they can differentiate into other types of immune cells such as macrophages and dendritic cells.

Monocytes play an important role in the body's defense against infection and tissue damage. They are able to engulf and digest foreign particles, microorganisms, and dead or damaged cells, which helps to clear them from the body. Monocytes also produce cytokines, which are signaling molecules that help to coordinate the immune response.

Elevated levels of monocytes in the bloodstream can be a sign of an ongoing infection, inflammation, or other medical conditions such as cancer or autoimmune disorders.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

Peptide mapping is a technique used in proteomics and analytical chemistry to analyze and identify the sequence and structure of peptides or proteins. This method involves breaking down a protein into smaller peptide fragments using enzymatic or chemical digestion, followed by separation and identification of these fragments through various analytical techniques such as liquid chromatography (LC) and mass spectrometry (MS).

The resulting peptide map serves as a "fingerprint" of the protein, providing information about its sequence, modifications, and structure. Peptide mapping can be used for a variety of applications, including protein identification, characterization of post-translational modifications, and monitoring of protein degradation or cleavage.

In summary, peptide mapping is a powerful tool in proteomics that enables the analysis and identification of proteins and their modifications at the peptide level.

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.

"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.

Affinity labels are chemical probes or reagents that can selectively and covalently bind to a specific protein or biomolecule based on its biological function or activity. These labels contain a functional group that interacts with the target molecule, often through non-covalent interactions such as hydrogen bonding, van der Waals forces, or ionic bonds. Once bound, the label then forms a covalent bond with the target molecule, allowing for its isolation and further study.

Affinity labels are commonly used in biochemistry and molecular biology research to identify and characterize specific proteins, enzymes, or receptors. They can be designed to bind to specific active sites, binding pockets, or other functional regions of a protein, allowing researchers to study the structure-function relationships of these molecules.

One example of an affinity label is a substrate analogue that contains a chemically reactive group. This type of affinity label can be used to identify and characterize enzymes by binding to their active sites and forming a covalent bond with the enzyme. The labeled enzyme can then be purified and analyzed to determine its structure, function, and mechanism of action.

Overall, affinity labels are valuable tools for studying the properties and functions of biological molecules in vitro and in vivo.

Respiratory burst is a term used in the field of biology, particularly in the context of immunology and cellular processes. It does not have a direct application to clinical medicine, but it is important for understanding certain physiological and pathophysiological mechanisms. Here's a definition of respiratory burst:

Respiratory burst is a rapid increase in oxygen consumption by phagocytic cells (like neutrophils, monocytes, and macrophages) following their activation in response to various stimuli, such as pathogens or inflammatory molecules. This process is part of the innate immune response and serves to eliminate invading microorganisms.

The respiratory burst involves the activation of NADPH oxidase, an enzyme complex present in the membrane of phagosomes (the compartment where pathogens are engulfed). Upon activation, NADPH oxidase catalyzes the reduction of oxygen to superoxide radicals, which then dismutate to form hydrogen peroxide. These reactive oxygen species (ROS) can directly kill or damage microorganisms and also serve as signaling molecules for other immune cells.

While respiratory burst is a crucial part of the immune response, excessive or dysregulated ROS production can contribute to tissue damage and chronic inflammation, which have implications in various pathological conditions, such as atherosclerosis, neurodegenerative diseases, and cancer.

A Structure-Activity Relationship (SAR) in the context of medicinal chemistry and pharmacology refers to the relationship between the chemical structure of a drug or molecule and its biological activity or effect on a target protein, cell, or organism. SAR studies aim to identify patterns and correlations between structural features of a compound and its ability to interact with a specific biological target, leading to a desired therapeutic response or undesired side effects.

By analyzing the SAR, researchers can optimize the chemical structure of lead compounds to enhance their potency, selectivity, safety, and pharmacokinetic properties, ultimately guiding the design and development of novel drugs with improved efficacy and reduced toxicity.

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.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

The Macrophage-1 Antigen (also known as Macrophage Antigen-1 or CD14) is a glycoprotein found on the surface of various cells, including monocytes, macrophages, and some dendritic cells. It functions as a receptor for complexes formed by lipopolysaccharides (LPS) and LPS-binding protein (LBP), which are involved in the immune response to gram-negative bacteria. CD14 plays a crucial role in activating immune cells and initiating the release of proinflammatory cytokines upon recognizing bacterial components.

In summary, Macrophage-1 Antigen is a cell surface receptor that contributes to the recognition and response against gram-negative bacteria by interacting with LPS-LBP complexes.

Molecular models are three-dimensional representations of molecular structures that are used in the field of molecular biology and chemistry to visualize and understand the spatial arrangement of atoms and bonds within a molecule. These models can be physical or computer-generated and allow researchers to study the shape, size, and behavior of molecules, which is crucial for understanding their function and interactions with other molecules.

Physical molecular models are often made up of balls (representing atoms) connected by rods or sticks (representing bonds). These models can be constructed manually using materials such as plastic or wooden balls and rods, or they can be created using 3D printing technology.

Computer-generated molecular models, on the other hand, are created using specialized software that allows researchers to visualize and manipulate molecular structures in three dimensions. These models can be used to simulate molecular interactions, predict molecular behavior, and design new drugs or chemicals with specific properties. Overall, molecular models play a critical role in advancing our understanding of molecular structures and their functions.

Formyltetrahydrofolates are a type of folate coenzyme that plays a crucial role in the metabolism of amino acids and nucleotides. They are formed from tetrahydrofolate, a reduced form of folic acid, by the addition of a one-carbon unit in the form of a formyl group (CHO). This process is catalyzed by the enzyme formyltetrahydrofolate synthetase.

Formyltetrahydrofolates are involved in several important metabolic pathways, including the synthesis of purines and pyrimidines, which are essential components of DNA and RNA. They also play a role in the methionine cycle, which is involved in the synthesis of various essential molecules such as neurotransmitters, phospholipids, and methyl groups required for DNA methylation.

Deficiencies in formyltetrahydrofolates or their precursors can lead to a variety of health problems, including megaloblastic anemia, neural tube defects, and cardiovascular disease. Therefore, it is important to ensure adequate intake of folate-rich foods or supplements, especially during pregnancy and in individuals with certain genetic polymorphisms that affect folate metabolism.

Cell degranulation is the process by which cells, particularly immune cells like mast cells and basophils, release granules containing inflammatory mediators in response to various stimuli. These mediators include histamine, leukotrienes, prostaglandins, and other chemicals that play a role in allergic reactions, inflammation, and immune responses. The activation of cell surface receptors triggers a signaling cascade that leads to the exocytosis of these granules, resulting in degranulation. This process is important for the immune system's response to foreign invaders and for the development of allergic reactions.

Brain Natriuretic Peptide (BNP) is a type of natriuretic peptide that is primarily produced in the heart, particularly in the ventricles. Although it was initially identified in the brain, hence its name, it is now known that the cardiac ventricles are the main source of BNP in the body.

BNP is released into the bloodstream in response to increased stretching or distension of the heart muscle cells due to conditions such as heart failure, hypertension, and myocardial infarction (heart attack). Once released, BNP binds to specific receptors in the kidneys, causing an increase in urine production and excretion of sodium, which helps reduce fluid volume and decrease the workload on the heart.

BNP also acts as a hormone that regulates various physiological functions, including blood pressure, cardiac remodeling, and inflammation. Measuring BNP levels in the blood is a useful diagnostic tool for detecting and monitoring heart failure, as higher levels of BNP are associated with more severe heart dysfunction.

NADPH oxidase is an enzyme complex that plays a crucial role in the production of reactive oxygen species (ROS) in various cell types. The primary function of NADPH oxidase is to catalyze the transfer of electrons from NADPH to molecular oxygen, resulting in the formation of superoxide radicals. This enzyme complex consists of several subunits, including two membrane-bound components (gp91phox and p22phox) and several cytosolic components (p47phox, p67phox, p40phox, and rac1 or rac2). Upon activation, these subunits assemble to form a functional enzyme complex that generates ROS, which serve as important signaling molecules in various cellular processes. However, excessive or uncontrolled production of ROS by NADPH oxidase has been implicated in the pathogenesis of several diseases, such as cardiovascular disorders, neurodegenerative diseases, and cancer.

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.

Leukotriene B4 (LTB4) is a type of lipid mediator called eicosanoid, which is derived from arachidonic acid through the 5-lipoxygenase pathway. It is primarily produced by neutrophils, eosinophils, monocytes, and macrophages in response to various stimuli such as infection, inflammation, or injury. LTB4 acts as a potent chemoattractant and activator of these immune cells, playing a crucial role in the recruitment and activation of neutrophils during acute inflammatory responses. It also enhances the adhesion of leukocytes to endothelial cells, contributing to the development of tissue damage and edema. Dysregulation of LTB4 production has been implicated in several pathological conditions, including asthma, atherosclerosis, and cancer.

CHO cells, or Chinese Hamster Ovary cells, are a type of immortalized cell line that are commonly used in scientific research and biotechnology. They were originally derived from the ovaries of a female Chinese hamster (Cricetulus griseus) in the 1950s.

CHO cells have several characteristics that make them useful for laboratory experiments. They can grow and divide indefinitely under appropriate conditions, which allows researchers to culture large quantities of them for study. Additionally, CHO cells are capable of expressing high levels of recombinant proteins, making them a popular choice for the production of therapeutic drugs, vaccines, and other biologics.

In particular, CHO cells have become a workhorse in the field of biotherapeutics, with many approved monoclonal antibody-based therapies being produced using these cells. The ability to genetically modify CHO cells through various methods has further expanded their utility in research and industrial applications.

It is important to note that while CHO cells are widely used in scientific research, they may not always accurately represent human cell behavior or respond to drugs and other compounds in the same way as human cells do. Therefore, results obtained using CHO cells should be validated in more relevant systems when possible.

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.

Complement receptors are proteins found on the surface of various cells in the human body, including immune cells and some non-immune cells. They play a crucial role in the complement system, which is a part of the innate immune response that helps to eliminate pathogens and damaged cells from the body. Complement receptors bind to complement proteins or fragments that are generated during the activation of the complement system. This binding triggers various intracellular signaling events that can lead to diverse cellular responses, such as phagocytosis, inflammation, and immune regulation.

There are several types of complement receptors, including:

1. CR1 (CD35): A receptor found on erythrocytes, B cells, neutrophils, monocytes, macrophages, and glomerular podocytes. It functions in the clearance of immune complexes and regulates complement activation.
2. CR2 (CD21): Expressed mainly on B cells and follicular dendritic cells. It facilitates antigen presentation, B-cell activation, and immune regulation.
3. CR3 (CD11b/CD18, Mac-1): Present on neutrophils, monocytes, macrophages, and some T cells. It mediates cell adhesion, phagocytosis, and intracellular signaling.
4. CR4 (CD11c/CD18, p150,95): Expressed on neutrophils, monocytes, macrophages, and dendritic cells. It is involved in cell adhesion, phagocytosis, and intracellular signaling.
5. C5aR (CD88): Found on various immune cells, including neutrophils, monocytes, macrophages, mast cells, eosinophils, and dendritic cells. It binds to the complement protein C5a and mediates chemotaxis, degranulation, and inflammation.
6. C5L2 (GPR77): Present on various cell types, including immune cells. Its function is not well understood but may involve regulating C5a-mediated responses or acting as a receptor for other ligands.

These receptors play crucial roles in the immune response and inflammation by mediating various functions such as chemotaxis, phagocytosis, cell adhesion, and intracellular signaling. Dysregulation of these receptors has been implicated in several diseases, including autoimmune disorders, infections, and cancer.

Cell migration inhibition refers to the process or agents that restrict the movement of cells, particularly in the context of cancer metastasis. Cell migration is a critical biological process involved in various physiological and pathological conditions, including embryonic development, wound healing, and tumor cell dissemination. Inhibiting cell migration can help prevent the spread of cancer to distant organs, thereby improving treatment outcomes and patient survival rates.

Various factors and mechanisms contribute to cell migration inhibition, such as:

1. Modulation of signaling pathways: Cell migration is regulated by complex intracellular signaling networks that control cytoskeletal rearrangements, adhesion molecules, and other components required for cell motility. Inhibiting specific signaling proteins or pathways can suppress cell migration.
2. Extracellular matrix (ECM) modifications: The ECM provides structural support and biochemical cues that guide cell migration. Altering the composition or organization of the ECM can hinder cell movement.
3. Inhibition of adhesion molecules: Cell-cell and cell-matrix interactions are mediated by adhesion molecules, such as integrins and cadherins. Blocking these molecules can prevent cells from attaching to their surroundings and migrating.
4. Targeting cytoskeletal components: The cytoskeleton is responsible for the mechanical forces required for cell migration. Inhibiting cytoskeletal proteins, such as actin or tubulin, can impair cell motility.
5. Use of pharmacological agents: Several drugs and compounds have been identified to inhibit cell migration, either by targeting specific molecules or indirectly affecting the overall cellular environment. These agents include chemotherapeutic drugs, natural compounds, and small molecule inhibitors.

Understanding the mechanisms underlying cell migration inhibition can provide valuable insights into developing novel therapeutic strategies for cancer treatment and other diseases involving aberrant cell migration.

Calcium signaling is the process by which cells regulate various functions through changes in intracellular calcium ion concentrations. Calcium ions (Ca^2+^) are crucial second messengers that play a critical role in many cellular processes, including muscle contraction, neurotransmitter release, gene expression, and programmed cell death (apoptosis).

Intracellular calcium levels are tightly regulated by a complex network of channels, pumps, and exchangers located on the plasma membrane and intracellular organelles such as the endoplasmic reticulum (ER) and mitochondria. These proteins control the influx, efflux, and storage of calcium ions within the cell.

Calcium signaling is initiated when an external signal, such as a hormone or neurotransmitter, binds to a specific receptor on the plasma membrane. This interaction triggers the opening of ion channels, allowing extracellular Ca^2+^ to flow into the cytoplasm. In some cases, this influx of calcium ions is sufficient to activate downstream targets directly. However, in most instances, the increase in intracellular Ca^2+^ serves as a trigger for the release of additional calcium from internal stores, such as the ER.

The release of calcium from the ER is mediated by ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs), which are activated by specific second messengers generated in response to the initial external signal. The activation of these channels leads to a rapid increase in cytoplasmic Ca^2+^, creating a transient intracellular calcium signal known as a "calcium spark" or "calcium puff."

These localized increases in calcium concentration can then propagate throughout the cell as waves of elevated calcium, allowing for the spatial and temporal coordination of various cellular responses. The duration and amplitude of these calcium signals are finely tuned by the interplay between calcium-binding proteins, pumps, and exchangers, ensuring that appropriate responses are elicited in a controlled manner.

Dysregulation of intracellular calcium signaling has been implicated in numerous pathological conditions, including neurodegenerative diseases, cardiovascular disorders, and cancer. Therefore, understanding the molecular mechanisms governing calcium homeostasis and signaling is crucial for the development of novel therapeutic strategies targeting these diseases.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Enzyme activation refers to the process by which an enzyme becomes biologically active and capable of carrying out its specific chemical or biological reaction. This is often achieved through various post-translational modifications, such as proteolytic cleavage, phosphorylation, or addition of cofactors or prosthetic groups to the enzyme molecule. These modifications can change the conformation or structure of the enzyme, exposing or creating a binding site for the substrate and allowing the enzymatic reaction to occur.

For example, in the case of proteolytic cleavage, an inactive precursor enzyme, known as a zymogen, is cleaved into its active form by a specific protease. This is seen in enzymes such as trypsin and chymotrypsin, which are initially produced in the pancreas as inactive precursors called trypsinogen and chymotrypsinogen, respectively. Once they reach the small intestine, they are activated by enteropeptidase, a protease that cleaves a specific peptide bond, releasing the active enzyme.

Phosphorylation is another common mechanism of enzyme activation, where a phosphate group is added to a specific serine, threonine, or tyrosine residue on the enzyme by a protein kinase. This modification can alter the conformation of the enzyme and create a binding site for the substrate, allowing the enzymatic reaction to occur.

Enzyme activation is a crucial process in many biological pathways, as it allows for precise control over when and where specific reactions take place. It also provides a mechanism for regulating enzyme activity in response to various signals and stimuli, such as hormones, neurotransmitters, or changes in the intracellular environment.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

Cell surface receptors, also known as membrane receptors, are proteins located on the cell membrane that bind to specific molecules outside the cell, known as ligands. These receptors play a crucial role in signal transduction, which is the process of converting an extracellular signal into an intracellular response.

Cell surface receptors can be classified into several categories based on their structure and mechanism of action, including:

1. Ion channel receptors: These receptors contain a pore that opens to allow ions to flow across the cell membrane when they bind to their ligands. This ion flux can directly activate or inhibit various cellular processes.
2. G protein-coupled receptors (GPCRs): These receptors consist of seven transmembrane domains and are associated with heterotrimeric G proteins that modulate intracellular signaling pathways upon ligand binding.
3. Enzyme-linked receptors: These receptors possess an intrinsic enzymatic activity or are linked to an enzyme, which becomes activated when the receptor binds to its ligand. This activation can lead to the initiation of various signaling cascades within the cell.
4. Receptor tyrosine kinases (RTKs): These receptors contain intracellular tyrosine kinase domains that become activated upon ligand binding, leading to the phosphorylation and activation of downstream signaling molecules.
5. Integrins: These receptors are transmembrane proteins that mediate cell-cell or cell-matrix interactions by binding to extracellular matrix proteins or counter-receptors on adjacent cells. They play essential roles in cell adhesion, migration, and survival.

Cell surface receptors are involved in various physiological processes, including neurotransmission, hormone signaling, immune response, and cell growth and differentiation. Dysregulation of these receptors can contribute to the development of numerous diseases, such as cancer, diabetes, and neurological disorders.

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.

I'm sorry for any confusion, but "Formates" is not a recognized term in medical terminology. It is possible that you may be referring to "formic acid" or "formate," which are terms used in chemistry and biochemistry. Formic acid is a colorless, pungent, and corrosive liquid with the chemical formula HCOOH. Its salts are called formates.

Formate is the anion (negatively charged ion) of formic acid, with the chemical formula HCOO-. Formate can be found in various biological systems and is involved in several metabolic processes. If you could provide more context or clarify your question, I would be happy to help further.

Vasoactive Intestinal Peptide (VIP) is a 28-amino acid polypeptide hormone that has potent vasodilatory, secretory, and neurotransmitter effects. It is widely distributed throughout the body, including in the gastrointestinal tract, where it is synthesized and released by nerve cells (neurons) in the intestinal mucosa. VIP plays a crucial role in regulating various physiological functions such as intestinal secretion, motility, and blood flow. It also has immunomodulatory effects and may play a role in neuroprotection. High levels of VIP are found in the brain, where it acts as a neurotransmitter or neuromodulator and is involved in various cognitive functions such as learning, memory, and social behavior.

N-Formylmethionine (fMet) is not a medical term per se, but rather a biochemical term. It is the formylated derivative of methionine, which is one of the twenty standard amino acids, and it plays a crucial role in the initiation of protein synthesis in prokaryotes and organelles of eukaryotic cells, such as mitochondria and chloroplasts.

In the context of medical research or clinical laboratory reports, you might encounter fMet in relation to bacterial infections, proteomics, or mitochondrial function. For example, formylated methionine residues on bacterial peptides can stimulate immune responses and are recognized by specific receptors on human immune cells, which can have implications for understanding infectious diseases and inflammation.

To provide a concise definition:
N-Formylmethionine (fMet) is the formylated derivative of methionine, primarily known for its role as the initiator amino acid in protein synthesis in prokaryotes and certain organelles of eukaryotic cells.

Amyloid beta-peptides (Aβ) are small protein fragments that are crucially involved in the pathogenesis of Alzheimer's disease. They are derived from a larger transmembrane protein called the amyloid precursor protein (APP) through a series of proteolytic cleavage events.

The two primary forms of Aβ peptides are Aβ40 and Aβ42, which differ in length by two amino acids. While both forms can be harmful, Aβ42 is more prone to aggregation and is considered to be the more pathogenic form. These peptides have the tendency to misfold and accumulate into oligomers, fibrils, and eventually insoluble plaques that deposit in various areas of the brain, most notably the cerebral cortex and hippocampus.

The accumulation of Aβ peptides is believed to initiate a cascade of events leading to neuroinflammation, oxidative stress, synaptic dysfunction, and neuronal death, which are all hallmarks of Alzheimer's disease. Although the exact role of Aβ in the onset and progression of Alzheimer's is still under investigation, it is widely accepted that they play a central part in the development of this debilitating neurodegenerative disorder.

Calcitonin gene-related peptide (CGRP) is a neurotransmitter and vasodilator peptide that is widely distributed in the nervous system. It is encoded by the calcitonin gene, which also encodes calcitonin and catestatin. CGRP is produced and released by sensory nerves and plays important roles in pain transmission, modulation of inflammation, and regulation of blood flow.

CGRP exists as two forms, α-CGRP and β-CGRP, which differ slightly in their amino acid sequences but have similar biological activities. α-CGRP is found primarily in the central and peripheral nervous systems, while β-CGRP is expressed mainly in the gastrointestinal tract.

CGRP exerts its effects by binding to specific G protein-coupled receptors, which are widely distributed in various tissues, including blood vessels, smooth muscles, and sensory neurons. Activation of CGRP receptors leads to increased intracellular cyclic AMP levels, activation of protein kinase A, and subsequent relaxation of vascular smooth muscle, resulting in vasodilation.

CGRP has been implicated in several clinical conditions, including migraine, cluster headache, and inflammatory pain. Inhibition of CGRP signaling has emerged as a promising therapeutic strategy for the treatment of these disorders.

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.

Cell-penetrating peptides (CPPs) are short, typically less than 30 amino acids long, biologically active peptides that have the ability to cross cell membranes and deliver various cargoes into cells. They were first discovered in the early 1990s and since then have gained significant attention due to their potential applications in drug delivery, gene therapy, and diagnostics.

CPPs can be classified into three categories based on their origin: (1) protein-derived CPPs, such as Tat from HIV-1 TAT protein and Penetratin from Drosophila Antennapedia protein; (2) chimeric CPPs, which are created by fusing different parts of various peptides; and (3) synthetic CPPs, which are designed and synthesized de novo.

The mechanism of cell penetration by CPPs is not fully understood but is thought to involve several processes, including endocytosis, direct translocation, and membrane disruption. The ability of CPPs to efficiently deliver various cargoes, such as proteins, nucleic acids, and small molecules, into cells has made them attractive tools for use in biomedical research and therapeutic applications. However, their potential cytotoxicity and lack of specificity remain major challenges that need to be addressed before they can be widely used in clinical settings.

Cricetinae is a subfamily of rodents that includes hamsters, gerbils, and relatives. These small mammals are characterized by having short limbs, compact bodies, and cheek pouches for storing food. They are native to various parts of the world, particularly in Europe, Asia, and Africa. Some species are popular pets due to their small size, easy care, and friendly nature. In a medical context, understanding the biology and behavior of Cricetinae species can be important for individuals who keep them as pets or for researchers studying their physiology.

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.

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.

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.

'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.

Further studies defined a receptor for the N-formyl oligopeptides, formyl peptide receptor (FPR), so named based on its ability ... The formyl peptide receptors (FPR) belong to a class of G protein-coupled receptors involved in chemotaxis. In humans, there ... Hence formyl peptide receptors are involved in mediating immune cell response to infection. These receptors may also act to ... Chemotaxis Receptors Migeotte I, Communi D, Parmentier M (Dec 2006). "Formyl peptide receptors: a promiscuous subfamily of G ...
Formyl peptide receptor 1 Formyl peptide receptor 2 N-Formylmethionine-leucyl-phenylalanine GRCh38: Ensembl release 89: ... Met-Val-D-Met inhibits human monocyte-derived dendritic cell maturation via formyl peptide receptor and formyl peptide receptor ... "Synthesis and use of a novel N-formyl peptide derivative to isolate a human N-formyl peptide receptor cDNA". Biochemical and ... N-formyl peptide receptor 3 (FPR3) is a receptor protein that in humans is encoded by the FPR3 gene. Confusingly, there are two ...
Eicosanoid receptor Formyl peptide receptor Lipoxin Resolvin Formyl peptide receptor 1 Formyl peptide receptor 3 GRCh38: ... and Formyl peptide receptor 3 (i.e. FPR3). FPR2 and FPR3 are termed formyl peptide receptors base on the similarities of their ... "House dust mite allergen activates human eosinophils via formyl peptide receptor and formyl peptide receptor-like 1". European ... "Synthesis and use of a novel N-formyl peptide derivative to isolate a human N-formyl peptide receptor cDNA". Biochemical and ...
... (FPR1, FPR1 receptor, fMet-Leu-Phe receptor 1, FMLP receptor 1, or N-formylmethionyl-leucyl- ... "Entrez Gene: Formyl peptide receptor 1". Migeotte I, Communi D, Parmentier M (Dec 2006). "Formyl peptide receptors: a ... "House dust mite allergen activates human eosinophils via formyl peptide receptor and formyl peptide receptor-like 1". European ... phenylalanine receptor 1) is a cell surface receptor protein that in humans is encoded by the formyl peptide receptor 1 (FPR1) ...
... formyl peptide receptor-like 1) - FPR2; receptor for Lipoxin A4 and 15-epi-Lipoxin A4 (or AT-LxA4) eicosanoids but also many ... Nomenclature for the formyl peptide receptor (FPR) family". Pharmacological Reviews. 61 (2): 119-61. doi:10.1124/pr.109.001578 ... The TP receptor is expressed in most human cells types as two alternatively spliced isoforms, TP receptor-α and TP receptor β, ... A final prostanoid receptor, DP2, is structurally related to the chemotaxis class of receptors and unlike the other prostanoid ...
Subsequently, Formyl peptide receptor 2 and Formyl peptide receptor 3 were also cloned based on the similarities in their amino ... acid sequence to that of formyl peptide receptor 1. Formyl peptide receptors 2 and 3 have very different abilities to bind and ... to formyl peptide receptor 1 and compared to each other and have very different functions than those of formyl peptide receptor ... The studies cited above lead to the eventual cloning of the human Formyl peptide receptor 1, a G protein coupled receptor that ...
Nomenclature for the formyl peptide receptor (FPR) family". Pharmacological Reviews. 61 (2): 119-61. doi:10.1124/pr.109.001578 ... FPR2, which is now termed the ALX, ALX/FPR, or ALX/FPR2 receptor, is a G protein coupled receptor initially identified as a ... LXA4 and 15-epi-LXA4 are high affinity receptor ligands for and activators of the FPR2 receptor. ... based on its amino acid sequence similarity to the known FMLP receptor, FPR1. At least six homologues of this receptor are ...
June 2009). "Formyl peptide receptors are candidate chemosensory receptors in the vomeronasal organ". Proceedings of the ... Recent studies proved a new family of formyl peptide receptor like proteins in VNO membranes of mice, which points to a close ... Rivière S, Challet L, Fluegge D, Spehr M, Rodriguez I (May 2009). "Formyl peptide receptor-like proteins are a novel family of ... These are G-protein-coupled receptors, which are often referred to as pheromone receptors since vomeronasal receptors have been ...
Rivière S, Challet L, Fluegge D, Spehr M, Rodriguez I (May 2009). "Formyl peptide receptor-like proteins are a novel family of ... Adrenergic receptor Olfactory receptors Receptor tyrosine kinases Epidermal growth factor receptor Insulin Receptor Fibroblast ... Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of ... Integrins Low Affinity Nerve Growth Factor Receptor NMDA receptor Several Immune receptors Toll-like receptor T cell receptor ...
"Real-time detection of implant-associated neutrophil responses using a formyl peptide receptor-targeting NIR nanoprobe". ...
... the agonist of formyl peptide receptor 3". Journal of Immunology. 187 (3): 1475-85. doi:10.4049/jimmunol.1003545. PMID 21709160 ... "Cathepsin D is present in human eccrine sweat and involved in the postsecretory processing of the antimicrobial peptide DCD-1L ...
... which is a natural ligand for formyl peptide receptor-like receptor 2 (FPRL2) and promotes calcium mobilization and chemotaxis ... the agonist of formyl peptide receptor 3". Journal of Immunology. 187 (3): 1475-85. doi:10.4049/jimmunol.1003545. PMID 21709160 ... the low-affinity N-formylpeptide receptor". Journal of Immunology. 178 (3): 1450-6. doi:10.4049/jimmunol.178.3.1450. PMID ... This protein includes a natural chemoattractant peptide of 21 amino acids at the N-terminus, ...
... formyl peptide receptor (60,000 receptor/cell) as well as the activator ability of its ligand formyl Met-Leu-Phe have been ... "Evidence for the presence of specific receptors for N-formyl chemotactic peptides on human spermatozoa". Journal of Clinical ... common signaling characters of the event is that a prototype of professional chemotaxis receptors, ...
"Evidence for the presence of specific receptors for N-formyl chemotactic peptides on human spermatozoa". J Clin Endocrinol ... Sperm find the eggs via chemotaxis, a type of ligand/receptor interaction. Resact is a 14 amino acid peptide purified from the ... In another ligand/receptor interaction, an oligosaccharide component of the egg binds and activates a receptor on the sperm and ... These receptors are unknown in mice but have been identified in guinea pigs.[citation needed] In mammals, the binding of the ...
Prossnitz ER, Ye RD (1997). "The N-formyl peptide receptor: a model for the study of chemoattractant receptor structure and ... In turn, the activation of these receptors functions to send the leukocytes to the site of infection and target the source of ... The expression of annexin A-II on the cell surface is believed to serve as a receptor for plasminogen, which functions to ... annexin A-I is believed to reduce inflammation of tissues by interacting with annexin A-I receptors on leukocytes. ...
... where he characterized trace amine-associated receptors and formyl peptide receptors. As an independent scientist, he has made ... "Evolution of sweet taste perception in hummingbirds by transformation of the ancestral umami receptor". Science. 345 (6199): ...
... differences between human and rabbit neutrophil receptors shown by the secretagogue activity of constrained formyl peptides". ... Using analysis of labeled β-glucuronidase peptides after hydrolysis of a substrate that enters a very stable intermediate stage ...
"A role of p44/42 mitogen-activated protein kinases in formyl-peptide receptor-mediated phospholipase D activity and oxidant ... receptor-mediated endocytosis, exocytosis, and cell migration. Through these processes, it has been further implicated in the ...
Bennett TA, Maestas DC, Prossnitz ER (August 2000). "Arrestin binding to the G protein-coupled N-formyl peptide receptor is ... Lefkowitz RJ (July 1998). "G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor ... "Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2 ... Arrestin beta 1 is a cytosolic protein and acts as a cofactor in the beta-adrenergic receptor kinase (BARK) mediated ...
... stimulates macrophage chemotaxis via formyl peptide receptor 1". BMB Reports. 48 (8): 479-484. doi:10.5483/BMBRep.2015.48.8.115 ... A peptide named S. s. mutilans venom toxin peptide (SsmTP) and S. s. mutilans 6 were identified in S. s. mutilans's venom. ... An antimicrobial peptide named scolopendrasin VII was discovered in S. s. mutilans . The peptide stimulates actin ... Scolopin 1 and 2 are antimicrobial peptides identified from the venom of S. s. mutilans. These peptides were identified by ...
"Dexras1/AGS-1 inhibits signal transduction from the Gi-coupled formyl peptide receptor to Erk-1/2 MAP kinases". The Journal of ... RASD1 is also reported to function with leptin in the activation of TRPC4 transient receptor potential channels and, thus, ... RASD1 could activate G proteins in a receptor-independent manner and inhibit signal transduction through several different G ... apparent disruption of receptor signaling complexes". The Journal of Biological Chemistry. 277 (16): 13827-30. doi:10.1074/jbc. ...
... as well as interaction with the formyl peptide receptor 2 (formylpeptide-like-1 receptor) have been published. Intracellular ... uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor". Journal of Immunology. 172 (11): 7078-85. ... The expressed peptide contains a three-turn α-helix, and has no symmetry. The length of the peptide depends on where it is ... Small humanin-like peptides are a group of peptides found in the mitochondrial 16S rRNA, and also possess retrograde signaling ...
These receptors include the G protein-coupled chemoattractant receptor FPR2 (formyl peptide receptor 2), believed to mediate ... The P2X7 purinergic receptor is another receptor used by SAA1 for a number of cellular functions including the activation of ... This effect is believed to be mediated through FPR2, a G protein-coupled chemoattractant receptor. The same receptor also ... Cai L, de Beer MC, de Beer FC, van der Westhuyzen DR (Jan 2005). "Serum amyloid A is a ligand for scavenger receptor class B ...
... formyl peptide receptor 1, and thereby activates phagocytes and presumably other cells bearing this receptor (see formyl ... is an activator of human phagocyte N-formyl peptide receptor". Blood. 93 (11): 3885-92. doi:10.1182/blood.V93.11.3885. PMID ... Enfuvirtide is a 36-amino acid peptide with the following sequence: CH3CO-Tyr-Thr-Ser-Leu-Ile-His-Ser-Leu-Ile-Glu-Glu-Ser-Gln- ... A biomimetic peptide, enfuvirtide was designed to mimic components of the HIV-1 fusion machinery and displace them, preventing ...
... leucyl-phenylalanine and other N-formylated oligopeptides which are made by bacteria and activate the formyl peptide receptor 1 ... There are at least three subclasses of monocytes in human blood based on their phenotypic receptors. Monocytes are amoeboid in ... The non-classical monocyte shows low level expression of CD14 and additional co-expression of the CD16 receptor (CD14+CD16++ ... as well as by binding to the microbe directly via pattern recognition receptors that recognize pathogens. Monocytes are also ...
"FAM19A4 is a novel cytokine ligand of formyl peptide receptor 1 (FPR1) and is able to promote the migration and phagocytosis of ...
... spinorphin blocks fMet-Leu-Phe-induced neutrophil chemotaxis by acting as a specific antagonist at the N-formylpeptide receptor ... Spinorphin is an endogenous, non-classical opioid peptide of the hemorphin family first isolated from the bovine spinal cord ( ... but it has been found to act as an antagonist of the P2X3 receptor, and as a weak partial agonist/antagonist of the FP1 ... a class of enzymes that break down endogenous the enkephalin peptides. It does so by inhibiting the enzymes aminopeptidase N ( ...
... also interacts with formyl peptide receptor 2 (FPR2) to form a complex that causes the microglia to release inflammatory ... Scavenger receptors are pattern recognition receptors (PRRs) found most commonly on immune cells. Their defining feature is ... February 1995). "Cloning of a novel bacteria-binding receptor structurally related to scavenger receptors and expressed in a ... Macrophage receptor with collagenous structure (MARCO) is a protein that in humans is encoded by the MARCO gene. MARCO is a ...
Delta toxin molecules activate a G-protein-coupled receptor expressed in leukocytes called formyl-peptide receptor 2 (FPR2), ... It is among other toxins produced by S. aureus and is part of the phenol-soluble modulin peptide family. Its alpha-helical, ... Delta toxin is also secreted from S. aureus without a signal peptide, but the toxin itself has been speculated to make an ... This reaction is only caused by delta toxin, rather than the other toxins produced by S. aureus, proving that PSM peptides have ...
For example, the Formyl peptide receptor 2 (FPL2 receptor) was initially suggested to be a second receptor with ~70% amino acid ... identity to Formyl peptide receptor 1 (FPL1 receptor). Both receptor types bind and are activated by a series of formylated ... Inhibition of BLT2 receptors by LY255283 but not of BLT1 receptors by U75302 and suppression of BLT2 receptors by siRNA ... BLT2 receptors, similar to BLT1 receptors, are G protein coupled receptors that, when ligand-bound, activate G proteins that ...
Further studies defined a receptor for the N-formyl oligopeptides, formyl peptide receptor (FPR), so named based on its ability ... The formyl peptide receptors (FPR) belong to a class of G protein-coupled receptors involved in chemotaxis. In humans, there ... Hence formyl peptide receptors are involved in mediating immune cell response to infection. These receptors may also act to ... Chemotaxis Receptors Migeotte I, Communi D, Parmentier M (Dec 2006). "Formyl peptide receptors: a promiscuous subfamily of G ...
N-Formyl peptide receptors (FPRs) are chemotactic receptors involved in inflammation. Three FPRs have been identified: FPR1, FPR2 ... N-FORMYL PEPTIDE RECEPTORS; UPAR; OXIDATIVE STRESS; SYSTEMIC SCLEROSIS. Settori scientifico-disciplinari del MIUR:. Area 06 - ... Napolitano, Filomena (2017) N-FORMYL PEPTIDE RECEPTORS AND UPAR FOSTER THE OXIDATIVE STRESS IN SYSTEMIC SCLEROSIS. [Tesi di ... N-FORMYL PEPTIDE RECEPTORS AND UPAR FOSTER THE OXIDATIVE STRESS IN SYSTEMIC SCLEROSIS. ...
"N-formyl peptide receptors internalize but do not recycle in the absence of arrestins." J Biol Chem, vol. 278, no. 43, Oct. ... "N-formyl peptide receptors internalize but do not recycle in the absence of arrestins." J Biol Chem 278, no. 43 (October 24, ... N-formyl peptide receptors internalize but do not recycle in the absence of arrestins.. Publication , Journal Article ... N-formyl peptide receptors internalize but do not recycle in the absence of arrestins. J Biol Chem. 2003 Oct 24;278(43):41581-4 ...
... Author: Weiss, Elisabeth; Kretschmer, Dorothee ...
The human N-formyl peptide receptor (FPR) is representative of a growing family of G protein-coupled receptors (GPCR) that ... such as receptor phosphorylation and ligand-induced receptor internalization. The results demonstrated that one of the mutants ... Receptor internalization was monitored by following the fate of the ligand as well as by directly monitoring the fate of the ... To reveal steps required for the activation of GPCR receptors, we utilized mutants of the FPR which have previously been shown ...
Human FPR2 (Formyl Peptide Receptor 2) CLIA Kit. E-CL-H0951 Regular price $650.00. $553.00 You Pay ...
... * QMRO Home ... Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders. ... Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders ...
These receptors also recognize host-derived chemotactic peptides in inflammation and injury. Here we report the capacity of ... Formylpeptide receptors mediate rapid neutrophil mobilization to accelerate wound healing. In: PloS one. 2014 ; Vol. 9, No. 3. ... Formylpeptide receptors mediate rapid neutrophil mobilization to accelerate wound healing. PloS one. 2014 Mar 6;9(3):e90613. ... Liu, M, Chen, K, Yoshimura, T, Liu, Y, Gong, W, Le, Y, Gao, JL, Zhao, J, Wang, JM & Wang, A 2014, Formylpeptide receptors ...
Human FPR2(Formyl Peptide Receptor 2) ELISA Kit. Human FPR2(Formyl Peptide Receptor 2) ELISA Kit ... Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Formyl Peptide Receptor 2 ... Human PDGFRb(Platelet Derived Growth Factor Receptor Beta) ELISA Kit. *Human C5b-9(Terminal Complement Complex C5b-9) ELISA Kit ... Human PDGFRa(Platelet Derived Growth Factor Receptor Alpha) ELISA Kit. *Human MASP2(Mannose Associated Serine Protease 2) ELISA ...
Acute cigarette smoke-induced eQTL affects formyl peptide receptor expression and lung function Pouwels, S. D., Wiersma, V. R. ...
N-formyl peptide receptor 2 (FPR2), a G-protein-coupled receptor, has been shown to be neuroprotective after stroke. FPR2 ... Role of N-formyl peptide receptor 2 in germinal matrix hemorrhage: an intrinsic review of a hematoma resolving pathway. ... Role of N-formyl peptide receptor 2 in germinal matrix hemorrhage: an intrinsic review of ... Recent literature suggests that FPR2 may play a role in the stimulation of scavenger receptor CD36. Scavenger receptor CD36 ...
... and bind to specific receptors on mammalian phagocytes. Since binding induces chemotaxis and ... Synthesis and use of a novel N-formyl peptide derivative to isolate a human N-formyl peptide receptor cDNA ... Synthesis and use of a novel N-formyl peptide derivative to isolate a human N-formyl peptide receptor cDNA ... A structural homologue of the N-formyl peptide receptor. Characterization and chromosome mapping of a peptide chemoattractant ...
Novel formyl peptide receptor (FPR) agonists with pyridinone and pyrimidindione scaffolds that are potentially useful for the ... Novel formyl peptide receptor (FPR) agonists with pyridinone and pyrimidindione scaffolds that are potentially useful for the ... such as N-formyl peptide receptor 2 (FPR2). FPRs represent potentially important therapeutic targets for the treatment of some ... such as N-formyl peptide receptor 2 (FPR2). FPRs represent potentially important therapeutic targets for the treatment of some ...
The Formyl Peptide Receptor 2 (FPR2) is a novel promising target. The Formyl Peptide Receptor 2 (FPR2) is a novel promising ...
Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1. Science 350, 972-978 (2015). This paper provides ... Vitamin D receptor deficiency enhances Wnt/β-catenin signaling and tumor burden in colon cancer. PLoS One 6, e23524 (2011). ... Bruce, D. & Cantorna, M.T. Intrinsic requirement for the vitamin D receptor in the development of CD8αα-expressing T cells. J. ... Saturated free fatty acids promote inflammation by binding to the Toll-like receptors TLR4 and TLR2 through the adaptor protein ...
Toll-like receptors (TLRs) enable innate immune cells, such as macrophages, to recognize a wide variety of microbial ligands, ... demonstrating that TLR2-EVs can act as decoy receptors. In summary, our data show that sTLR2 and full-length TLR2 are released ... TLR2 was upregulated in a GC receptor-dependent manner, as shown by Western blot and qPCR. Furthermore, long-term ... TLR2 was upregulated in a GC receptor-dependent manner, as shown by Western blot and qPCR. Furthermore, long-term ...
Biased perspectives on formyl peptide receptors (CRC 1009 project A06). Ursula Rescher, Institute of Medical Biochemistry, WWU ... A biased view on formyl peptide receptor activation (CRC 1009 A06). Ursula Rescher, Institute of Medical Biochemistry, ZMBE ... Atypical Chemokine Receptor 4? What is a nice receptor like you doing in places like these?. Antal Rot, Queen Mary University ...
SAA is a functional agonist for formyl peptide receptor 2 (FPR2/ALX), where it promotes chemotaxis and survival of neutrophils ... SAA is a functional agonist for formyl peptide receptor 2 (FPR2/ALX), where it promotes chemotaxis and survival of neutrophils ... Nomenclature for the formyl peptide receptor (FPR) family. Pharmacol Rev. (2009) 61:119-61. doi: 10.1124/pr.109.001578 ... SAA is a functional agonist for formyl peptide receptor 2 (FPR2/ALX), where it promotes chemotaxis and survival of neutrophils ...
4-Aroyl-3-hydroxy-5-phenyl-1H-pyrrol-2(5H)-ones as N-Formyl Peptide Receptor 1 (FPR1) Antagonists. Biochemical Pharmacology. ... Antagonism of human formyl peptide receptor 1 with natural compounds and their synthetic derivatives. International ... Synthesis of Five- and Six-Membered N-Phenylacetamido Substituted Heterocycles as Formyl Peptide Receptor Agonists. BJCP- ... Development of Small Molecule Non-peptide Formyl Peptide Receptor (FPR) Ligands and Molecular Modeling of Their Recognition. ...
Inhibition of formyl peptide receptors improves the outcome in a mouse model of Alzheimer disease. Schröder N, Schaffrath A, ... The formyl peptide receptor agonist Ac2-26 alleviates neuroinflammation in a mouse model of pneumococcal meningitis. Rüger M, ... The N-Formyl Peptide Receptor 2 (FPR2) Agonist MR-39 Exhibits Anti-Inflammatory Activity in LPS-Stimulated Organotypic ... Toll-Like Receptor 2-Mediated Glial Cell Activation in a Mouse Model of Cuprizone-Induced Demyelination. Esser S, Göpfrich L, ...
Czapiga M, Gao JL, Kirk A, Lekstrom-Himes J. Human platelets exhibit chemotaxis using functional N-formyl peptide receptors. ... These NFPs are a chemoattractant for host phagocytes and can be recognised by formyl peptide receptors on the plasma membrane [ ... and will therefore be recognised by the same formyl peptide receptors. In addition, detection of the extracellular ... These DAMPs include succinate, N-formyl peptides, dsRNA, mtDNA, ROS, cardiolipin, and ATP. Loss or exposure of these DAMPs ...
Journal Article] Synergetic roles of Formyl Peptide Receptor 1 oligomerization in ligand-induced signal transduction2020. *. ... Presentation] Transient dimer formation of G-protein coupled receptor: single fluorescent molecule imaging in live cells2018. * ... Journal Article] The Class-A GPCR Dopamine D2 Receptor Forms Transient Dimers Stabilized by Agonists: Detection by Single- ...
Various chemoattractants, such as N -formyl peptides (eg, FMLP), C5a, [13] leukotriene B4, and platelet-activating factor (PAF ... Many chemotactic factor receptors are coupled to G proteins and, when activated, cause phospholipase C activation, which then ... IP3 binds to specific receptors on intracellular membranes, resulting in the release of intracellular calcium, which is rapidly ... Secretory vesicles contain alkaline phosphatase, cytochrome b558, and N-formyl-1-methionyl-1-leucyl-1-phenylalamine (FMLP) ...
... have clarified a decades-old enigma surrounding receptor molecule behaviors. ... ... Using formyl-peptide receptors (FPRs) as a model GPCR, the research team found that the two views are both partially correct. ... Tags development, g protein coupled receptors, journal of cell biology, kyoto university Normal air could halve fuel ... Expanding drug development horizons: Receptor behaviors observed in living cell membranes. February 7, 2011. ScienceBlog.com ...
The expression of FPR2 receptor, known to mediate the activity of pro-resolving mediators was also increased in mice lacking ... RT-PCR studies allowed us to quantify the expression of N-formyl peptide receptor 2 (FPR2), key RvD1 receptor [10], in the ... Ong, W.Y.; Chua, J.J.E. Role of formyl peptide receptor 2 (FPR2) in the normal brain and in neurological conditions. Neural. ... Lack of formyl peptide receptor 1 and 2 leads to more severe inflammation and higher mortality in mice with of pneumococcal ...
Role of formyl peptide receptor 2 in homing of endothelial progenitor cells and therapeutic angiogenesis. Advances in ... receptor-1 or Flt-1 [19, 20], CD133 or prominine-1 (surface glycoprotein), Tie-2 (endothelial receptor tyrosine kinase), Von ... and its effects are dependent on the activation of the CXCR4 receptor. VEGF exerts its effect via tyrosine kinase receptors, ... Effects of an angiotensin II receptor blocker on the impaired function of endothelial progenitor cells in patients with ...
CYCLOPROPYL UREA FORMYL PEPTIDE 2 RECEPTOR AND FORMYL PEPTIDE 1 RECEPTOR AGONISTS. ... Examples of amine protecting groups include, but are not limited to, the following: 1) acyl types such as formyl, ... "The Peptides: Analysis, Synthesis, Biology, Vol. 3, Academic Press, New York, (1981), the disclosure of which is hereby ...
Formyl Peptide Receptor 1 Modulates Endothelial Cell Functions by NADPH Oxidase-Dependent VEGFR2 Transactivation. Cattaneo F, ... Peptide Science. 2018 pp: e24037. Apoptin-derived peptide reverses cisplatin resistance in gastric cancer through the PI3K-AKT ... Preparation and cellular uptake of bicyclic-peptide cargo clicked to cell penetrating peptides. Kulkarni K, Watson G, Sang J, ... ATL3 Is a Tubular ER-Phagy Receptor for GABARAP-Mediated Selective Autophagy. Chen Q, Xiao Y, Chai P, Zheng P, Teng J, et. al. ...
2012Shear-induced resistance to neutrophil activation via the formyl peptide receptorBiophys J. 102:1804-1814 ... 2020Neutrophil chemoattractant receptors in health and disease: double-edged swordsCell Mol Immunol. 17:433-450 ... 2F). These hits suggest that the cell swelling cascade begins with fMLP binding to the chemoattractant receptor FPR1, which ... 2C). This effect depends on chemoattractant-based cell stimulation, as knockout of the fMLP receptor FPR1 completely inhibits ...
C. X. Qin, L. T. May, R. Li et al., "Small-molecule-biased formyl peptide receptor agonist compound 17b protects against ... Another study regarding small molecule agonists of formyl peptide receptors (FPRs) in MIRI also suggested that the activation ... of the potential inflammatory pathways of chemerin-derived peptides/proteins suggested that the ligand-receptor interaction ... The spontaneously elevated adenosine receptor A2BR found in myocardium during MIRI may exert an infarct-limiting effect in the ...
  • In humans, there are three formyl peptide receptor isoforms, each encoded by a separate gene that are named FPR1, FPR2, and FPR3. (wikipedia.org)
  • Two receptors where thereafter discovered and named FPR1 and FPR2 based on the similarity of their genes' predicted amino acid sequence to that of FPR rather than on any ability to bind or be activated by the formyl oligopeptides. (wikipedia.org)
  • Two G protein-coupled formylpeptide receptors Fpr1 and Fpr2 mediate rapid neutrophil infiltration in the liver of Listeria-infected mice by sensing pathogen-derived chemotactic ligands. (elsevierpure.com)
  • Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Formyl Peptide Receptor 2 (FPR2) in samples from Tissue homogenates, cell lysates and other biological fluids with no significant corss-reactivity with analogues from other species. (jsce-ip.com)
  • N- formyl peptide receptor 2 (FPR2), a G-protein-coupled receptor , has been shown to be neuroprotective after stroke . (bvsalud.org)
  • Recent literature suggests that FPR2 may play a role in the stimulation of scavenger receptor CD36. (bvsalud.org)
  • The resolution of inflammation is an active response involving the interaction of pro-resolving mediators with specific receptors, such as N-formyl peptide receptor 2 (FPR2). (unifi.it)
  • SAA is a functional agonist for formyl peptide receptor 2 (FPR2/ALX), where it promotes chemotaxis and survival of neutrophils. (frontiersin.org)
  • In human, the FPR family consists mainly of three receptors, FPR1, FPR2/ALX (formerly FPRL1), and FPR3 (formerly FPRL2) which all couple to the G i subtype of G-proteins and ultimately lead to the activation of phospholipase C and intracellular Ca 2+ increase. (alomone.com)
  • The formyl peptide receptors (FPR) belong to a class of G protein-coupled receptors involved in chemotaxis. (wikipedia.org)
  • Arrestins mediate phosphorylation-dependent desensitization, internalization, and initiation of signaling cascades for the majority of G protein-coupled receptors (GPCRs). (duke.edu)
  • The human N-formyl peptide receptor (FPR) is representative of a growing family of G protein-coupled receptors (GPCR) that respond to chemokines and chemoattractants. (unm.edu)
  • That these observations may be of more general importance in GPCR-mediated signaling is suggested by the highly conserved nature of the mutants studied: D71, R123, and the site represented by amino acids 309-311 are very highly conserved throughout the entire superfamily of G protein-coupled receptors. (unm.edu)
  • The work focuses on G protein-coupled receptors (GPCRs), a class of molecules in cell membranes that comprise the largest superfamily in the human genome. (scienceblog.com)
  • The research program focuses on the molecular mechanisms controlling the function of the largest family of drug targets, the G protein-coupled receptors (GPCR). (umontreal.ca)
  • These peptides are released from bacteria during infection and activate formyl peptide receptor (FPR), a member of G-protein coupled receptors (GPCRs). (alomone.com)
  • G-protein coupled receptors (GPCRs), located on the cell surface, play an important role in this communication. (lu.se)
  • Her fields of interest include: G protein-coupled receptor signalling, biased signalling and selectivity, compartmentalised G protein signalling, bioluminescence resonance energy transfer (BRET)-based technology. (qub.ac.uk)
  • Then, she quickly developed a marked interest for G protein-coupled receptor (GPCR) signalling. (qub.ac.uk)
  • Scholars@Duke publication: Changes in actin state and chemotactic peptide receptor expression in granulocytes during cytokine administration after autologous bone marrow transplantation. (duke.edu)
  • We studied the changes in actin state and chemotactic peptide receptor expression in granulocytes from patients receiving different cytokines following high dose chemotherapy and autologous bone marrow transplantation (ABMT). (duke.edu)
  • The chemotactic peptide receptor expression was significantly higher in patients treated with ABMT alone or ABMT plus G-CSF. (duke.edu)
  • To reveal steps required for the activation of GPCR receptors, we utilized mutants of the FPR which have previously been shown to be incapable of binding and activating G proteins. (unm.edu)
  • Using formyl-peptide receptors (FPRs) as a model GPCR, the research team found that the two views are both partially correct. (scienceblog.com)
  • This promotes G protein uncoupling from receptor, GPCR internalisation and signalling arrest. (qub.ac.uk)
  • Studies conducted in the 1970s found that a series of N-Formylmethionine-containing oligopeptides, including the most potent and best known member of this series, N-formylmethionine-leucyl-phenylalanine (fMLF or fMet-Leu-Phe), stimulated rabbit and human neutrophils by an apparent receptor-dependent mechanism to migrate in a directional pattern in classical laboratory assays of chemotaxis. (wikipedia.org)
  • Our research group is mainly focusing on the interplay of different circulating molecules and receptors involved in inflammation, such as formyl peptide and toll-like receptors, on the surface of platelets, monocytes, and neutrophils, and how they control multicellular interactions and complex functions during the inflammatory responses. (reading.ac.uk)
  • Here, we report that exposure to glucose in diabetic range results in impaired chemotaxis signaling through the formyl peptide receptor (FPR) in neutrophils, culminating in reduced chemotaxis and delayed neutrophil trafficking in the wound of Lepr db (db/db) type 2 diabetic mice, rendering diabetic wound vulnerable to infection. (elifesciences.org)
  • With respect to binding of the formyl Met-Leu-Phe peptide, there are additional potential interactions which include hydrogen bonding interactions between Arg84 and Lys85 of the first extracellular loop and the N-formyl group of the ligand as well as the peptide backbone of formyl Met-Leu-Phe which can form similar interactions. (wikipedia.org)
  • The formyl-Met moiety of the ligand was shown to form disulfide bridges with Cys residues, and an interaction with Arg163 was also demonstrated. (wikipedia.org)
  • It is important to mention that some interaction which stabilize the conformation of the receptor may also influence ligand-binding. (wikipedia.org)
  • These components can also determine or make more specific the ligand-receptor interaction. (wikipedia.org)
  • For this study, the FPR mutants were expressed in human myeloid U937 cells and characterized for functions in addition to G protein coupling, such as receptor phosphorylation and ligand-induced receptor internalization. (unm.edu)
  • Receptor internalization was monitored by following the fate of the ligand as well as by directly monitoring the fate of the receptor. (unm.edu)
  • von der Weid B, Rossier D, Lindup M, Tuberosa J, Widmer A, Col JD, Kan C, Carleton A , Rodriguez I . Large-scale transcriptional profiling of chemosensory neurons identifies receptor-ligand pairs in vivo. (neurotree.org)
  • Cells synthesize and release signalling molecules (ligands), which produce a specific response only in those cells that have a receptor for that ligand. (lu.se)
  • The dendrigraft polylysine (DGL) with its uniform size and multifunctional groups was employed as the polymeric core and conjugated with platinum-based compounds as therapeutics and WKYMVm peptide (Wpep) as a targeting ligand to construct the novel delivery platform Wpep-DGL/Pt. (thno.org)
  • N-Formyl peptide receptors (FPRs) are chemotactic receptors involved in inflammation. (unina.it)
  • Several functions of FPRs occur through the interaction with the chemotactic domain (residues 88SRSRY92) of the urokinase-type plasminogen activator receptor (uPAR). (unina.it)
  • Novel formyl peptide receptor (FPR) agonists with pyridinone and pyrimidindione scaffolds that are potentially useful for the treatment of rheumatoid arthritis / Crocetti L. (unifi.it)
  • Consistent with this, neutrophil chemotaxis in vitro and neutrophil mobilization into peripheral blood in vivo in response to the prototype N -formylpeptide fMLF (formyl-methionyl-leucyl-phenylalanine) were both absent in FPR −/− mice. (silverchair.com)
  • Perhaps the most widely used probes for studying mechanisms of leukocyte chemotaxis are the N -formylpeptides, particularly the prototype formyl-methionyl-leucyl-phenylalanine (fMLF). (silverchair.com)
  • Although the basal level of F-actin was high following ABMT, granulocytes from all patients showed an additional increase in F-actin content after stimulation with either the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) or phorbol myristate acetate (PMA). (duke.edu)
  • Since these oligopeptides were produced by bacteria or synthetic analogs of such products, it was suggested that the N-formyl oligopeptides are important chemotatic factors and their receptors are important chemotactic factor receptors that act respectively as signaling and signal-recognizing elements to initiate inflammation responses in order to defend against bacterial invasion. (wikipedia.org)
  • These receptors also recognize host-derived chemotactic peptides in inflammation and injury. (elsevierpure.com)
  • Toll-like receptors (TLRs) enable innate immune cells, such as macrophages, to recognize a wide variety of microbial ligands, thereby promoting inflammation. (frontiersin.org)
  • The receptor displays a high homology to chemoattractant-like receptors involved in inflammation processes. (lu.se)
  • The selectin adhesion molecules and chemoattractant receptors synergistically regulate leukocyte migration into lymphoid tissues and sites of inflammation, but little is known about how these families of receptors modulate each other's function. (upenn.edu)
  • The close phylogenetic relation of signaling in chemotaxis and olfaction was recently proved by detection formyl peptide receptor like proteins as a distinct family of vomeronasal organ chemosensors in mice. (wikipedia.org)
  • Many GPCRs undergo agonist-mediated internalization through arrestin-dependent mechanisms, wherein arrestin serves as an adapter between the receptor and endocytic proteins. (duke.edu)
  • N -formylpeptides derive from bacterial and mitochondrial proteins, and bind to specific receptors on mammalian phagocytes. (silverchair.com)
  • Receptor-stimulated guanine-nucleotide-triphosphate binding to guanine-nucleotide-binding regulatory proteins. (eurekamag.com)
  • The data thus provide evidence for an essential difference between GTP[S] and p[NH]ppG binding to guanine-nucleotide-binding regulatory proteins and suggest that, in addition to the nucleotide-exchange reaction, a (thio)phosphate-group-transfer process via guanine-nucleotide-binding regulatory protein beta subunits is involved in the receptor-stimulated binding of guanine nucleotide triphosphates to guanine-nucleotide-binding regulatory proteins. (eurekamag.com)
  • As GPCRs represent the largest family of cell surface proteins, and control a vast repertoire of physiological functions, these receptors are the actual target of 30-50% of all prescribed drugs. (qub.ac.uk)
  • NFPs are mainly found in bacteria where formyl modified methionine initiates protein synthesis [ 7 ]. (nature.com)
  • Due to its bacterial ancestry, mitochondrial formylation of methionine is required for translation initiation of mtDNA-derived mRNA [ 7 ] and will therefore be recognised by the same formyl peptide receptors. (nature.com)
  • Chemotactic factors from both Gram-positive and Gram-negative bacteria are short peptides with N-formyl methionine at the N-terminus. (alomone.com)
  • Among the neutrophil activating factors, mitochondrial-derived N-formyl methionine (fMet) has been reported in several autoinflammatory conditions. (lu.se)
  • Since binding induces chemotaxis and activation of phagocytes in vitro, it has been postulated that N -formylpeptide receptor signaling in vivo may be important in antimicrobial host defense, although direct proof has been lacking. (silverchair.com)
  • Hence formyl peptide receptors are involved in mediating immune cell response to infection. (wikipedia.org)
  • Sequence is implicated in osseous and cartilage development, and the receptor is also suggested to have a pathophysiological role as one of the co-receptors involved in human and simian immunodeficiency virus (HIV-1 and SIV)-infection of CD4+ immune cells. (lu.se)
  • We further show that at least some auxiliary receptors remain functional under diabetic conditions and their engagement by the pro-inflammatory cytokine CCL3, overrides the requirement for FPR signaling and substantially improves infection control by jumpstarting the neutrophil trafficking toward infection, and stimulates healing in diabetic wound. (elifesciences.org)
  • Scavenger receptor CD36 plays a vital role in microglia phagocytic blood clot clearance after germinal matrix hemorrhage . (bvsalud.org)
  • Wound healing is a multi-phased pathophysiological process requiring chemoattractant receptor-dependent accumulation of myeloid cells in the lesion. (elsevierpure.com)
  • These NFPs are a chemoattractant for host phagocytes and can be recognised by formyl peptide receptors on the plasma membrane [ 8 , 9 ]. (nature.com)
  • Genomic organization and promoter analysis of the gene encoding the mouse chemoattractant-like receptor, CMKLR1. (lu.se)
  • Interactions between L-selectin and chemoattractant receptors were therefore examined using transfected rat basophilic leukemia cell lines (RBL-2H3) that expressed human L-selectin along with human leukocyte chemoattractant receptors. (upenn.edu)
  • Scholars@Duke publication: N-formyl peptide receptors internalize but do not recycle in the absence of arrestins. (duke.edu)
  • Here we test this hypothesis in mice lacking the high affinity N -formylpeptide receptor (FPR), created by targeted gene disruption. (silverchair.com)
  • 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. (bvsalud.org)
  • These receptors were originally identified by their ability to bind N-formyl peptides such as N-formylmethionine produced by the degradation of either bacterial or host cells. (wikipedia.org)
  • While the FPR was able to recycle in the wild type cells, receptor recycling was largely absent in the arrestin double knockout cells. (duke.edu)
  • In addition, the presence of EVs reduced inflammatory responses in Pam 3 CSK 4 -treated endothelial cells and HEK Dual reporter cells, demonstrating that TLR2-EVs can act as decoy receptors. (frontiersin.org)
  • beta, gamma-imino]triphosphate, p[NH]ppG, and the regulation of binding by the formyl-peptide-receptor agonist, fMet-Leu-Phe, were studied in membranes of differentiated HL-60 cells. (eurekamag.com)
  • Ackels T , von der Weid B, Rodriguez I , Spehr M . Physiological characterization of formyl peptide receptor expressing cells in the mouse vomeronasal organ. (neurotree.org)
  • By using nonlinear regression analysis, it was revealed that A549 epithelial cells have two receptors for LL-37B, with high and low affinity for LL-37, respectively. (ed.ac.uk)
  • Certain scavenger receptors can internalize micro-organisms as well as apoptotic cells. (bvsalud.org)
  • This study lead to the identification of the ghrelin receptor-induced biased signalling mediated by a new compound responsible for unique physiological outcomes observed in murine model. (qub.ac.uk)
  • Mouse TIG2/chemerin was found to activate the mouse receptor, although to a lower degree than for the human receptor. (lu.se)
  • Peptides corresponding to the C-terminus of mouse TIG2/chemerin could activate mouse CMKLR1/ChemR23 but to a lower extent than the human receptor. (lu.se)
  • The results indicate that the peptide domains necessary for receptor activation differ for human and mouse TIG2/chemerin or that the maximal response of the mouse receptor is lower than in human. (lu.se)
  • The mouse chemerin receptor gene, mcmklr1, utilizes alternative promoters for transcription and is regulated by all-trans retinoic acid. (lu.se)
  • Among certain better-characterized co-receptors, the HIV-1 co-receptor function of CMKLR1/ChemR23 resembles that of the chemokine receptor, CCR3. (lu.se)
  • Then, Dr Plouffe completed a PhD in Neuroscience at University of Ottawa (ON, Canada) (2006-2011), where she identified the molecular mechanisms involved in the opposite regulation of dopamine D1 and D5 receptors by protein kinase C. Her work shed light on the mechanisms underlying the positive action of prefrontal cortex on motor activity and of the thalamic parafascicular nucleus on awareness. (qub.ac.uk)
  • She started her journey in this exciting research field by investigating the molecular mechanisms involved in the angiotensin type 2 receptor (AT 2 R)-mediated neurite outgrowth as a MSc student (2003-2005). (qub.ac.uk)
  • They represent the first line of defense against pathogens in the lower airspace and recognize microbial ligands via pattern recognition receptors ( 4 , 5 ). (frontiersin.org)
  • Toll-like receptors (TLRs) are the major pattern recognition receptors of the innate immune system that sense a wide range of "danger" signals or pathogen-associated molecular patterns (PAMPs) ( 6 - 8 ). (frontiersin.org)
  • LL-37 is a human cationic host defense peptide that is an essential component of innate immunity. (ed.ac.uk)
  • A large group of structurally diverse cell surface receptors that mediate endocytic uptake of modified LIPOPROTEINS. (bvsalud.org)
  • Using a "humanized" hybrid rat CMKLR1/ChemR23 receptor as model, it was shown that the major determinants for HIV-1 and HIV-2 interaction with the receptor reside to a varying degree in the N-terminus and second extracellular loop, whereas the viral interaction in the case of SIV primarily involves the second extracellular loop. (lu.se)
  • These DAMPs include mitochondrial DNA (mtDNA), cardiolipin, N-formyl peptides (NFPs), and reactive oxygen species (ROS) but also metabolites such as adenosine triphosphate (ATP) and succinate [ 3 ]. (nature.com)
  • This was one of the rare studies translating biased signalling from a receptor to in vivo functions. (qub.ac.uk)
  • Here, we observed that HDL isolated from healthy individuals inhibited the production of inflammatory cytokines by peripheral monocytes stimulated with a Toll-like receptor 2 agonist. (lww.com)
  • These observations indicate that, although the FPR can internalize in the absence of arrestins, recycling of internalized receptors to the cell surface is prevented. (duke.edu)
  • The importance of human CMKLR1/ChemR23 as a co-receptor for HIV and SIV has been investigated. (lu.se)
  • Diverse signal recognition receptors and signal transduction pathways were defined which regulate cellular functions, metabolism and development. (mdpi.com)
  • These receptors may also act to suppress the immune system under certain conditions. (wikipedia.org)
  • Despite the importance of this receptor class to immune function, relatively little is known about the molecular mechanisms involved in their activation. (unm.edu)
  • Further studies defined a receptor for the N-formyl oligopeptides, formyl peptide receptor (FPR), so named based on its ability to bind and become activated by the oligopeptides. (wikipedia.org)
  • Multiple activation steps of the N-formyl peptide receptor. (unm.edu)
  • Models of receptor activation based on the observed results are discussed. (unm.edu)
  • Department of Pharmacology and Toxicology, School of Medicine, Universidad Complutense de Madrid (UCM), Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), Instituto de Investigación Neuroquímica (IUINQ-UCM), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Avda. (mdpi.com)
  • Kyoto, Japan - Unprecedented single molecule imaging movies of living cell membranes, taken by a research team based at Kyoto University and the University of New Mexico, have clarified a decades-old enigma surrounding receptor molecule behaviors. (scienceblog.com)
  • In contrast, TLR2 was upregulated in a GC receptor-dependent manner, as shown by Western blot and qPCR. (frontiersin.org)
  • We have described the genomic organization of cmklr1 in mouse and analysed the regulatory mechanism behind the corresponding receptor expression. (lu.se)
  • The formyl peptide receptor (FPR) belongs to the class of receptors possessing seven hydrophobic transmembrane domains. (wikipedia.org)