The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants.
Mononuclear phagocytes derived from bone marrow precursors but resident in the peritoneum.
Round, granular, mononuclear phagocytes found in the alveoli of the lungs. They ingest small inhaled particles resulting in degradation and presentation of the antigen to immunocompetent cells.
The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).
A mononuclear phagocyte colony-stimulating factor (M-CSF) synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (RECEPTOR, MACROPHAGE COLONY-STIMULATING FACTOR).
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.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
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.
Proteins released by sensitized LYMPHOCYTES and possibly other cells that inhibit the migration of MACROPHAGES away from the release site. The structure and chemical properties may vary with the species and type of releasing cell.
Established cell cultures that have the potential to propagate indefinitely.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the STOMACH. The two sacs are connected by the foramen of Winslow, or epiploic foramen.
Organic esters of thioglycolic acid (HS-CH2COOH).
Heparin-binding proteins that exhibit a number of inflammatory and immunoregulatory activities. Originally identified as secretory products of MACROPHAGES, these chemokines are produced by a variety of cell types including NEUTROPHILS; FIBROBLASTS; and EPITHELIAL CELLS. They likely play a significant role in respiratory tract defenses.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Surface antigens expressed on myeloid cells of the granulocyte-monocyte-histiocyte series during differentiation. Analysis of their reactivity in normal and malignant myelomonocytic cells is useful in identifying and classifying human leukemias and lymphomas.
The serous fluid of ASCITES, the accumulation of fluids in the PERITONEAL CAVITY.
A receptor for MACROPHAGE COLONY-STIMULATING FACTOR encoded by the c-fms proto-oncogene (GENES, FMS). It contains an intrinsic protein-tyrosine kinase activity. When activated the receptor undergoes autophosphorylation, phosphorylation of down-stream signaling molecules and rapid down-regulation.
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.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification.
A family of scavenger receptors that mediate the influx of LIPIDS into MACROPHAGES and are involved in FOAM CELL formation.
Membrane-bound cytoplasmic vesicles formed by invagination of phagocytized material. They fuse with lysosomes to form phagolysosomes in which the hydrolytic enzymes of the lysosome digest the phagocytized material.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place.
A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES.
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.
An encapsulated lymphatic organ through which venous blood filters.
Factors secreted by stimulated lymphocytes that prime macrophages to become nonspecifically cytotoxic to tumors. They also modulate the expression of macrophage cell surface Ia antigens. One MAF is INTERFERON-GAMMA. Other factors antigenically distinct from IFN-gamma have also been identified.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues.
A subclass of lectins that are specific for CARBOHYDRATES that contain MANNOSE.
A chemokine that is a chemoattractant for MONOCYTES and may also cause cellular activation of specific functions related to host defense. It is produced by LEUKOCYTES of both monocyte and lymphocyte lineage and by FIBROBLASTS during tissue injury. It has specificity for CCR2 RECEPTORS.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
A large group of structurally diverse cell surface receptors that mediate endocytic uptake of modified LIPOPROTEINS. Scavenger receptors are expressed by MYELOID CELLS and some ENDOTHELIAL CELLS, and were originally characterized based on their ability to bind acetylated LOW-DENSITY LIPOPROTEINS. They can also bind a variety of other polyanionic ligand. Certain scavenger receptors can internalize micro-organisms as well as apoptotic cells.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
A pattern recognition receptor that interacts with LYMPHOCYTE ANTIGEN 96 and LIPOPOLYSACCHARIDES. It mediates cellular responses to GRAM-NEGATIVE BACTERIA.
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.
A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.
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.
A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.
The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.
Elements of limited time intervals, contributing to particular results or situations.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Washing liquid obtained from irrigation of the lung, including the BRONCHI and the PULMONARY ALVEOLI. It is generally used to assess biochemical, inflammatory, or infection status of the lung.
Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C; (CHEMOKINES, C); CC; (CHEMOKINES, CC); and CXC; (CHEMOKINES, CXC); according to variations in a shared cysteine motif.
A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Cells that can carry out the process of PHAGOCYTOSIS.
A CC chemokine with specificity for CCR5 RECEPTORS. It is a chemoattractant for NK CELLS; MONOCYTES and a variety of other immune cells. This chemokine is encoded by multiple genes.
A CC chemokine with specificity for CCR1 RECEPTORS and CCR5 RECEPTORS. It is a chemoattractant for NK CELLS; MONOCYTES; and a variety of other immune cells. This chemokine is encoded by multiple genes.
Proteins prepared by recombinant DNA technology.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A ureahydrolase that catalyzes the hydrolysis of arginine or canavanine to yield L-ornithine (ORNITHINE) and urea. Deficiency of this enzyme causes HYPERARGININEMIA. EC
The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.
Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.
A pattern recognition receptor that forms heterodimers with other TOLL-LIKE RECEPTORS. It interacts with multiple ligands including PEPTIDOGLYCAN, bacterial LIPOPROTEINS, lipoarabinomannan, and a variety of PORINS.
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
The number of CELLS of a specific kind, usually measured per unit volume or area of sample.
The bovine variety of the tubercle bacillus. It is called also Mycobacterium tuberculosis var. bovis.
Soluble mediators of the immune response that are neither antibodies nor complement. They are produced largely, but not exclusively, by monocytes and macrophages.
Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate.
The engulfing of liquids by cells by a process of invagination and closure of the cell membrane to form fluid-filled vacuoles.
A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation.
Glycoproteins found on the membrane or surface of cells.
Thickening and loss of elasticity of the walls of ARTERIES of all sizes. There are many forms classified by the types of lesions and arteries involved, such as ATHEROSCLEROSIS with fatty lesions in the ARTERIAL INTIMA of medium and large muscular arteries.
A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.
Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).
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.
The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A superfamily of large integral ATP-binding cassette membrane proteins whose expression pattern is consistent with a role in lipid (cholesterol) efflux. It is implicated in TANGIER DISEASE characterized by accumulation of cholesteryl ester in various tissues.
A CXC chemokine that is synthesized by activated MONOCYTES and NEUTROPHILS. It has specificity for CXCR2 RECEPTORS.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
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.
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.
A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.
A species of gram-positive, rod-shaped bacteria widely distributed in nature. It has been isolated from sewage, soil, silage, and from feces of healthy animals and man. Infection with this bacterium leads to encephalitis, meningitis, endocarditis, and abortion.
Specialized phagocytic cells of the MONONUCLEAR PHAGOCYTE SYSTEM found on the luminal surface of the hepatic sinusoids. They filter bacteria and small foreign proteins out of the blood, and dispose of worn out red blood cells.
Antibodies produced by a single clone of cells.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A species of gram-negative, aerobic bacteria that is the causative agent of LEGIONNAIRES' DISEASE. It has been isolated from numerous environmental sites as well as from human lung tissue, respiratory secretions, and blood.
A secreted matrix metalloproteinase which is highly expressed by MACROPHAGES where it may play a role in INFLAMMATION and WOUND HEALING.
A bacterium causing tuberculosis in domestic fowl and other birds. In pigs, it may cause localized and sometimes disseminated disease. The organism occurs occasionally in sheep and cattle. It should be distinguished from the M. avium complex, which infects primarily humans.
Culture media containing biologically active components obtained from previously cultured cells or tissues that have released into the media substances affecting certain cell functions (e.g., growth, lysis).
A CD antigen that contains a conserved I domain which is involved in ligand binding. When combined with CD18 the two subunits form MACROPHAGE-1 ANTIGEN.
Adherence of cells to surfaces or to other cells.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Leukocyte differentiation antigens and major platelet membrane glycoproteins present on MONOCYTES; ENDOTHELIAL CELLS; PLATELETS; and mammary EPITHELIAL CELLS. They play major roles in CELL ADHESION; SIGNAL TRANSDUCTION; and regulation of angiogenesis. CD36 is a receptor for THROMBOSPONDINS and can act as a scavenger receptor that recognizes and transports oxidized LIPOPROTEINS and FATTY ACIDS.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.
The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The rate dynamics in chemical or physical systems.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.
A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents.
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
Assays that measure the rate of migration of MACROPHAGES. They may involve the use hollow plastic chamber, sealed at one end with a porous membrane and suspended over a larger well which may contain CHEMOTACTIC FACTORS. The migration of cell through the pores to the other side of the membrane is measured.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
A sialic acid binding lectin that was originally identified as an adhesion molecule for inflammatory MACROPHAGES and activated MONOCYTES. This protein is the largest known siglec subtype and contains 16 immunoglobulin C2-set domains. It plays a role in cell to cell interactions and interactions with BACTERIA.
An intracellular signaling adaptor protein that plays a role in TOLL-LIKE RECEPTOR and INTERLEUKIN 1 RECEPTORS signal transduction. It forms a signaling complex with the activated cell surface receptors and members of the IRAK KINASES.
The movement of cells or organisms toward or away from a substance in response to its concentration gradient.
Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis.
Salts of nitrous acid or compounds containing the group NO2-. The inorganic nitrites of the type MNO2 (where M=metal) are all insoluble, except the alkali nitrites. The organic nitrites may be isomeric, but not identical with the corresponding nitro compounds. (Grant & Hackh's Chemical Dictionary, 5th ed)
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
Substances that reduce or suppress INFLAMMATION.
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
A family of scavenger receptors that are predominately localized to CAVEOLAE of the PLASMA MEMBRANE and bind HIGH DENSITY LIPOPROTEINS.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
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.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
A genus of flagellate protozoa comprising several species that are pathogenic for humans. Organisms of this genus have an amastigote and a promastigote stage in their life cycles. As a result of enzymatic studies this single genus has been divided into two subgenera: Leishmania leishmania and Leishmania viannia. Species within the Leishmania leishmania subgenus include: L. aethiopica, L. arabica, L. donovani, L. enrietti, L. gerbilli, L. hertigi, L. infantum, L. major, L. mexicana, and L. tropica. The following species are those that compose the Leishmania viannia subgenus: L. braziliensis, L. guyanensis, L. lainsoni, L. naiffi, and L. shawi.
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.
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.
A bacteria isolated from normal skin, intestinal contents, wounds, blood, pus, and soft tissue abscesses. It is a common contaminant of clinical specimens, presumably from the skin of patients or attendants.
Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, QUARTZ, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid.
Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.
Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.
A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.
Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells.
An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.
Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.
An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC
Cell surface proteins that bind lipoproteins with high affinity. Lipoprotein receptors in the liver and peripheral tissues mediate the regulation of plasma and cellular cholesterol metabolism and concentration. The receptors generally recognize the apolipoproteins of the lipoprotein complex, and binding is often a trigger for endocytosis.
CCR receptors with specificity for CHEMOKINE CCL2 and several other CCL2-related chemokines. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; MACROPHAGES; BASOPHILS; and NK CELLS.
Infections with bacteria of the genus LISTERIA.
Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include INTERLEUKIN-3; (IL-3); GRANULOCYTE COLONY-STIMULATING FACTOR; (G-CSF); MACROPHAGE COLONY-STIMULATING FACTOR; (M-CSF); and GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; (GM-CSF).
Mice bearing mutant genes which are phenotypically expressed in the animals.
A milky, product excreted from the latex canals of a variety of plant species that contain cauotchouc. Latex is composed of 25-35% caoutchouc, 60-75% water, 2% protein, 2% resin, 1.5% sugar & 1% ash. RUBBER is made by the removal of water from latex.(From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed). Hevein proteins are responsible for LATEX HYPERSENSITIVITY. Latexes are used as inert vehicles to carry antibodies or antigens in LATEX FIXATION TESTS.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Transport proteins that carry specific substances in the blood or across cell membranes.
A parasitic hemoflagellate of the subgenus Leishmania leishmania that infects man and animals including rodents. The Leishmania mexicana complex causes both cutaneous (LEISHMANIASIS, CUTANEOUS) and diffuse cutaneous leishmaniasis (LEISHMANIASIS, DIFFUSE CUTANEOUS) and includes the subspecies amazonensis, garnhami, mexicana, pifanoi, and venezuelensis. L. m. mexicana causes chiclero ulcer, a form of cutaneous leishmaniasis (LEISHMANIASIS, CUTANEOUS) in the New World. The sandfly, Lutzomyia, appears to be the vector.
Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.
Enzymes of the isomerase class that catalyze the oxidation of one part of a molecule with a corresponding reduction of another part of the same molecule. They include enzymes converting aldoses to ketoses (ALDOSE-KETOSE ISOMERASES), enzymes shifting a carbon-carbon double bond (CARBON-CARBON DOUBLE BOND ISOMERASES), and enzymes transposing S-S bonds (SULFUR-SULFUR BOND ISOMERASES). (From Enzyme Nomenclature, 1992) EC 5.3.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
A parasitic hemoflagellate of the subgenus Leishmania leishmania that infects man and animals and causes visceral leishmaniasis (LEISHMANIASIS, VISCERAL). The sandfly genera Phlebotomus and Lutzomyia are the vectors.
A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.
A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells.
An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.
A CC-type chemokine that is a chemoattractant for EOSINOPHILS; MONOCYTES; and LYMPHOCYTES. It is a potent and selective eosinophil chemotaxin that is stored in and released from PLATELETS and activated T-LYMPHOCYTES. Chemokine CCL5 is specific for CCR1 RECEPTORS; CCR3 RECEPTORS; and CCR5 RECEPTORS. The acronym RANTES refers to Regulated on Activation, Normal T Expressed and Secreted.
Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity.
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
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.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Animals or humans raised in the absence of a particular disease-causing virus or other microorganism. Less frequently plants are cultivated pathogen-free.
A cytokine subunit that is a component of both interleukin-12 and interleukin-23. It binds to the INTERLEUKIN-12 SUBUNIT P35 via a disulfide bond to form interleukin-12 and to INTERLEUKIN-23 SUBUNIT P19 to form interleukin-23.
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.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
A broad category of receptor-like proteins that may play a role in transcriptional-regulation in the CELL NUCLEUS. Many of these proteins are similar in structure to known NUCLEAR RECEPTORS but appear to lack a functional ligand-binding domain, while in other cases the specific ligands have yet to be identified.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.

Hypersensitivity pneumonitis: experimental production in calves with antigens of Micropolyspora faeni. (1/32182)

Pneumonitis was induced in calves by exposure to aerosols of Micropolyspora faeni with or without prior sensitization of the animals by subcutaneous injection of antigen. The pneumonitis primarily involved centrolobular areas and was characterized by alveolar septal thickening and loss of air space by cellular infiltration. Vasculitis and focal haemorrhage occurred in certain individuals and haemoproteinaceous exudate appeared within septa and alveolar lumina. The pneumonitis was compared with human farmer's lung, pneumonitis of housed cattle and other experimental hypersensitivity pneumonitides.  (+info)

Cell-mediated immunity: dealing a direct blow to pathogens. (2/32182)

Cytotoxic T lymphocytes are essential for defence against viral infections. Recent data demonstrating direct killing of intracellular bacteria by granulysin, a protein released from the granules of cytotoxic T lymphocytes, emphasize the contribution of these lymphocytes to the control of tuberculosis.  (+info)

Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages. (3/32182)

Both chlamydial and human heat shock protein 60s (HSP 60), which colocalize in human atheroma, may contribute to inflammation during atherogenesis. We tested the hypothesis that chlamydial or human HSP 60 activates human endothelial cells (ECs), smooth muscle cells (SMCs), and monocyte-derived macrophages. We examined the expression of adhesion molecules such as endothelial-leukocyte adhesion molecule-1 (E-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), and the production of the proinflammatory cytokine interleukin-6 (IL-6). We also tested whether either HSP 60 induces nuclear factor-kappaB (NF-kappaB), which contributes to the gene expression of these molecules. Either chlamydial or human HSP 60 induced E-selectin, ICAM-1, and VCAM-1 expression on ECs similar to levels induced by Escherichia coli lipopolysaccharide (LPS). Each HSP 60 also significantly induced IL-6 production by ECs, SMCs, and macrophages to an extent similar to that induced by E. coli LPS, as assessed by enzyme-linked immunosorbent assay (ELISA). In ECs, either HSP 60 triggered activation of NF-kappaB complexes containing p65 and p50 Rel proteins. Heat treatment abolished all these effects, but did not alter the ability of E. coli LPS to induce these functions. Chlamydial and human HSP 60s therefore activate human vascular cell functions relevant to atherogenesis and lesional complications. These findings help to elucidate the mechanisms by which a chronic asymptomatic chlamydial infection might contribute to the pathophysiology of atheroma.  (+info)

Anti-monocyte chemoattractant protein-1/monocyte chemotactic and activating factor antibody inhibits neointimal hyperplasia in injured rat carotid arteries. (4/32182)

Monocyte chemoattractant protein-1 (MCP-1)/monocyte chemotactic and activating factor (MCAF) has been suggested to promote atherogenesis. The effects of in vivo neutralization of MCP-1 in a rat model were examined in an effort to clarify the role of MCP-1 in the development of neointimal hyperplasia. Competitive polymerase chain reaction analysis revealed maximum MCP-1 mRNA expression at 4 hours after carotid arterial injury. Increased immunoreactivities of MCP-1 were also detected at 2 and 8 hours after injury. Either anti-MCP-1 antibody or nonimmunized goat IgG (10 mg/kg) was then administered every 12 hours to rats that had undergone carotid arterial injury. Treatment with 3 consecutive doses of anti-MCP-1 antibody within 24 hours (experiment 1) and every 12 hours for 5 days (experiment 2) significantly inhibited neointimal hyperplasia at day 14, resulting in a 27.8% reduction of the mean intima/media ratio (P<0.05) in experiment 1 and a 43.6% reduction (P<0.01) in experiment 2. This effect was still apparent at day 56 (55.6% inhibition; P<0.05). The number of vascular smooth muscle cells in the neointima at day 4 was significantly reduced by anti-MCP-1 treatment, demonstrating the important role of MCP-1 in early neointimal lesion formation. However, recombinant MCP-1 did not stimulate chemotaxis of vascular smooth muscle cells in an in vitro migration assay. These results suggest that MCP-1 promotes neointimal hyperplasia in early neointimal lesion formation and that neutralization of MCP-1 before, and immediately after, arterial injury may be effective in preventing restenosis after angioplasty. Further studies are needed to clarify the mechanism underlying the promotion of neointimal hyperplasia by MCP-1.  (+info)

Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. (5/32182)

Nigrostriatal dopaminergic neurons undergo sprouting around the margins of a striatal wound. The mechanism of this periwound sprouting has been unclear. In this study, we have examined the role played by the macrophage and microglial response that follows striatal injury. Macrophages and activated microglia quickly accumulate after injury and reach their greatest numbers in the first week. Subsequently, the number of both cell types declines rapidly in the first month and thereafter more slowly. Macrophage numbers eventually cease to decline, and a sizable group of these cells remains at the wound site and forms a long-term, highly activated resident population. This population of macrophages expresses increasing amounts of glial cell line-derived neurotrophic factor mRNA with time. Brain-derived neurotrophic factor mRNA is also expressed in and around the wound site. Production of this factor is by both activated microglia and, to a lesser extent, macrophages. The production of these potent dopaminergic neurotrophic factors occurs in a similar spatial distribution to sprouting dopaminergic fibers. Moreover, dopamine transporter-positive dopaminergic neurites can be seen growing toward and embracing hemosiderin-filled wound macrophages. The dopaminergic sprouting that accompanies striatal injury thus appears to result from neurotrophic factor secretion by activated macrophages and microglia at the wound site.  (+info)

Overexpression of CuZn superoxide dismutase protects RAW 264.7 macrophages against nitric oxide cytotoxicity. (6/32182)

Initiation of nitric oxide (NO.)-mediated apoptotic cell death in RAW 264.7 macrophages is associated with up-regulation of mitochondrial manganese superoxide dismutase (MnSOD; SOD2) and down-regulation of cytosolic copper zinc superoxide dismutase (CuZnSOD; SOD1) at their individual mRNA and protein levels. To evaluate the decreased CuZnSOD expression and the initiation of apoptosis we stably transfected macrophages to overexpress human CuZnSOD. Individual clones revealed a 2-fold increase in CuZnSOD activity. Expression of a functional and thus protective CuZnSOD was verified by attenuated superoxide (O2(.)-)-mediated apoptotic as well as necrotic cell death. In this study we showed that SOD-overexpressing macrophages (R-SOD1-12) were also protected against NO.-initiated programmed cell death. Protection was substantial towards NO. derived from exogenously added NO donors or when NO. was generated by inducible NO synthase activation, and was evident at the level of p53 accumulation, caspase activation and DNA fragmentation. Stimulation of parent and SOD-overexpressing cells with a combination of lipopolysaccharide and murine interferon gamma produced equivalent amounts of nitrite/nitrate, which ruled out attenuated inducible NO. synthase activity during protection. Because protection by a O2(.)--scavenging system during NO. -intoxication implies a role of NO. and O2(.)- in the progression of cell damage, we used uric acid to delineate the role of peroxynitrite during NO.-elicited apoptosis. The peroxynitrite scavenger uric acid left S-nitrosoglutathione or spermine-NO-elicited apoptosis unaltered, blocking only 3-morpholinosydnonimine-mediated cell death. As a result we exclude peroxynitrite from contributing, to any major extent, to NO. -mediated apoptosis. Therefore protection observed with CuZnSOD overexpression is unlikely to stem from interference with peroxynitrite formation and/or action. Unequivocally, the down-regulation of CuZnSOD is associated with NO. cytotoxicity, whereas CuZnSOD overexpression protects macrophages from apoptosis.  (+info)

Salmonella typhimurium and lipopolysaccharide stimulate extracellularly regulated kinase activation in macrophages by a mechanism involving phosphatidylinositol 3-kinase and phospholipase D as novel intermediates. (7/32182)

Activation of the extracellularly regulated kinase (ERK) pathway is part of the early biochemical events that follow lipopolysaccharide (LPS) treatment of macrophages or their infection by virulent and attenuated Salmonella strains. Phagocytosis as well as the secretion of invasion-associated proteins is dispensable for ERK activation by the pathogen. Furthermore, the pathways used by Salmonella and LPS to stimulate ERK are identical, suggesting that kinase activation might be solely mediated by LPS. Both stimuli activate ERK by a mechanism involving herbimycin-dependent tyrosine kinase(s) and phosphatidylinositol 3-kinase. Phospholipase D activation and stimulation of protein kinase C appear to be intermediates in this novel pathway of MEK/ERK activation.  (+info)

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. (8/32182)

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)

Fingerprint Dive into the research topics of Selenoproteome Identification in Inflamed Murine Primary Bone Marrow-Derived Macrophages by Nano-LC Orbitrap Fusion Tribrid Mass Spectrometry. Together they form a unique fingerprint. ...
The hallmark of the human atherosclerotic plaque is the presence of lipid-laden macrophages, or foam cells. However, many macrophage subsets are found within atherosclerotic lesions and it is not well understood how monocytes differentiate into these subsets. We focused on characterizing macrophages derived in vitro from human peripheral blood monocytes treated with IL-15, IL-4 or IL-10. We show these macrophages to have differing phenotypes: CD209+CD64+, CD209+CD23+, or CD209+CD163+ for macrophages derived from IL-15, IL-4, or IL-10 respectively. To characterize the macrophage subsets ability to become foam cells we measured their uptake of fluorescently-labeled oxidized LDL (oxLDL). IL-10 derived macrophages had the greatest amount of oxLDL uptake. We then investigated the mechanism of uptake and found that fucoidan, a class-A scavenger receptor competitor, significantly inhibited uptake of oxLDL in IL-10 cells. On the other hand a blocking antibody against the class B scavenger receptor, ...
Toll-like receptors (TLRs) and macrophages play an important role in rheumatoid arthritis (RA). Currently, it is not clear whether inflammatory M1 or anti-inflammatory M2 predominate among the resident macrophages in the synovium. In the present study, we set out to investigate the impact of TLR stimulation on monocyte-derived M1 and M2 macrophage function and phenotype by mimicking the exposure to abundant TLR agonists as occurs in the context of RA. The response of macrophage subsets to TLR2 and TLR4 activation was evaluated on cluster of differentiation (CD) marker profile; cytokine secretion; gene expression; and NF-κB, interferon regulatory factors 3 and 7 (IRF3/7), and mitogen-activated protein kinase (MAPK) activation. Human monocytes were isolated from peripheral blood of healthy individuals and patients with RA and differentiated into M1-like and M2-like macrophages by granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), respectively.
TY - JOUR. T1 - BCL6 suppresses RhoA activity to alter macrophage morphology and motility. AU - Pixley, Fiona J.. AU - Xiong, Ying. AU - Yu, Raymond Yick Loi. AU - Sahai, Erik A.. AU - Stanley, E. Richard. AU - Ye, B. Hilda. PY - 2005/5/1. Y1 - 2005/5/1. N2 - BCL6 is a potent transcriptional repressor that plays important roles in germinal center formation, T helper cell differentiation and lymphomagenesis and regulates expression of several chemokine genes in macrophages. In a further investigation of its role in macrophages, we show that BCL6 inactivation in primary bone marrow-derived macrophages leads to decreased polarization, motility and cell spreading accompanied by an increase in peripheral focal complexes, anchored F-actin bundles and cortical F-actin density. These changes were associated with excess RhoA activation. C3 transferase inhibition of RhoA activity reverted the adhesion structure phenotype, which was not affected by Rho kinase inhibitors, suggesting that other downstream ...
Chemotaxis assays are an invaluable tool for studying the biological activity of inflammatory mediators such as CC chemokines, which have been implicated in a wide range of chronic inflammatory diseases. Conventional chemotaxis systems such as the modified Boyden chamber are limited in terms of the data captured given that the assays are analysed at a single time-point. We report the optimisation and validation of a label-free, real-time cell migration assay based on electrical cell impedance to measure chemotaxis of different primary murine macrophage populations in response to a range of CC chemokines and other chemoattractant signalling molecules. We clearly demonstrate key differences in the migratory behavior of different murine macrophage populations and show that this dynamic system measures true macrophage chemotaxis rather than chemokinesis or fugetaxis. We highlight an absolute requirement for Gαi signaling and actin cytoskeletal rearrangement as demonstrated by Pertussis toxin and
Mycobacterium tuberculosis and Mycobacterium leprae, the causative agents of tuberculosis and leprosy, respectively, produce large quantities of lipoarabinomannan (LAM), a highly immunogenic, cell wall-associated glycolipid. This molecule has been previously reported to be a potent inhibitor of gamma interferon-mediated activation of murine macrophages. Studies of the mechanism by which this mycobacterial glycolipid down-regulates macrophage effector functions provide evidence that LAM acts at several levels and that it can (i) scavenge potentially cytotoxic oxygen free radicals, (ii) inhibit protein kinase C activity, and (iii) block the transcriptional activation of gamma interferon-inducible genes in human macrophage-like cell lines. These results suggest that LAM can inhibit macrophage activation and triggering and cytocidal activity and that it may represent a chemically defined virulence factor contributing to the persistence of mycobacteria within mononuclear phagocytes. ...
Gaucher disease is caused by an inherited deficiency of glucocerebrosidase that manifests with storage of glycolipids in lysosomes, particularly in macrophages. Available cell lines modeling Gaucher disease do not demonstrate lysosomal storage of glycolipids; therefore, we set out to develop two macrophage models of Gaucher disease that exhibit appropriate substrate accumulation. We used these cellular models both to investigate altered macrophage biology in Gaucher disease and to evaluate candidate drugs for its treatment. We generated and characterized monocyte-derived macrophages from 20 patients carrying different Gaucher disease mutations. In addition, we created induced pluripotent stem cell (iPSC)-derived macrophages from five fibroblast lines taken from patients with type 1 or type 2 Gaucher disease. Macrophages derived from patient monocytes or iPSCs showed reduced glucocerebrosidase activity and increased storage of glucocerebroside and glucosylsphingosine in lysosomes. These ...
Infections caused by organisms of the Mycobacterium avium complex occur in approximately 50 to 60% of patients with AIDS. M. avium is an intracellular pathogen that survives and multiplies within mononuclear phagocytes. In this study, we investigated the uptake of M. avium grown within macrophages (intracellular growth M. avium [IG]) by a second macrophage compared with M. avium cultured in broth (extracellular growth M. avium [EG]). The results showed that IG was six- to eightfold more efficient than EG in entering macrophages. In addition, while an anti-CR3 antibody was able to inhibit approximately 60% of EG uptake by macrophages, it failed to inhibit the entry of IG. In contrast to EG, IG uptake into macrophages was significantly inhibited in the presence of anti-beta1-integrin and anti-transferrin receptor antibodies. Entry into macrophages by alternate receptors was associated with resistance to tumor necrosis factor alpha (TNF-alpha) stimulation. While stimulation with TNF-alpha resulted ...
TY - JOUR. T1 - Distinct macrophage phenotypes in allergic and nonallergic lung inflammation. AU - Robbe, Patricia. AU - Draijer, Christina. AU - Borg, Thiago. AU - Luinge, Marjan. AU - Timens, Wim AU - Wouters, IM. AU - Melgert, Barbro. AU - Hylkema, MN. PY - 2015/2/15. Y1 - 2015/2/15. N2 - Chronic exposure to farm environments is a risk factor for nonallergic lung disease. In contrast to allergic asthma, in which type 2 helper T cell (Th2) activation is dominant, exposure to farm dust extracts (FDE) induces Th1/Th17 lung inflammation, associated with neutrophil infiltration. Macrophage influx is a common feature of both types of lung inflammation, allergic and nonallergic. However, macrophage functions and phenotypes may vary according to their polarized state, which is dependent on the cytokine environment. In this study, we aimed to characterize and quantify the lung macrophage populations in two established murine models of allergic and nonallergic lung inflammation by means of ...
The heterogeneity of myeloid-derived cells is a well-known phenomenon in cancer (46-48), wound healing (5, 7), and was recently also described in sterile CNS trauma (10, 11). In this study, such heterogeneity was demonstrated in an autoimmune pathological condition within the CNS, autoimmune uveitis. This diversity was manifested in this study by the presence of resident microglia, as well as infiltrating monocyte-derived macrophages in the uveitic retina, the latter being recruited only upon disease induction. Moreover, within the infiltrating macrophage population, we identified different phenotypic subsets, the frequencies of which changed along the disease course, and which appeared to have distinct functional effects, contributing differentially to disease induction and resolution. The fact that specific depletion of the infiltrating macrophages, when performed at the resolution phase, resulted in impaired EAU resolution indicates that monocyte-derived macrophages performed a role that ...
It is widely known that macrophages can be activated to kill tumor cells. It is also known that tumor-infiltrating macrophages can be immunosuppressed. The mechanisms of both tumor killing by activated macrophages and tumor-induced macrophage suppression are not entirely clear. To better understand the mechanisms that macrophages use to kill tumor cells, a murine macrophage cell line, RAW264.7, was fixed with paraformaldehyde, subsequently stimulated with lipopolysaccharide (LPS) and co-cultured with tumor cells. Macrophage activity was assessed by nitric oxide (NO) production and tumor cell growth inhibition in the 3H-thymidine incorporation assay. It was found that fixed macrophages were still able to suppress the proliferation of tumor cells while the production of NO was abrogated. Additionally, a model of tumor-induced suppression of macrophages was developed by co-culturing them with tumor cell conditioned media before adding LPS. Inhibition of macrophage activity by tumor cell products ...
In this study we immunophenotypically differentiate subpopulations of brain macrophages into perivascular macrophages and parenchymal microglia and demonstrate that perivascular macrophages are the major cell productively infected by SIV in the CNS of macaques. Preferential infection of perivascular macrophages in the CNS may account for several important observations concerning infection of the CNS, viral dynamics in the CNS, and the role of the CNS as a viral sanctuary or reservoir.. Although it has not been directly demonstrated, it is generally assumed that lentiviruses enter the CNS by the traffic of infected monocyte/macrophages (64). Our data showing that perivascular macrophages are the major cell type, infected in the brain, support this hypothesis. Studies in chimeric rodents and humans receiving bone marrow indicate that perivascular macrophages are continuously replaced from the circulation (15)(16)(17)(43). The immunophenotype described for perivascular macrophages, ...
Inflammation is associated with macrophage activation, and this process has been shown to occur during atherogenesis. Macrophages (J774A.1) that were activated with either lipopolysaccharide (LPS), zymosan, or phorbol ester demonstrated a 30-35% increased uptake and degradation of low density lipoprotein (LDL) in comparison with nonactivated cells. This phenomenon was also shown for LDL cellular binding, and it resulted in macrophage cholesterol accumulation, as evidenced by cholesterol mass determination and flow cell cytometric analysis. Enhanced uptake of LDL was also obtained with two other types of macrophages: mouse peritoneal macrophages and human monocyte-derived macrophages. In LPS-stimulated macrophages, high density lipoprotein-mediated cholesterol efflux was not different from that shown in nonstimulated cells. Cellular cholesterol synthesis, however, was increased by 25% in the activated macrophages. Macrophage activation, measured as cellular procoagulant activity, was higher in ...
TY - JOUR. T1 - Lentivirus delivery of IL-10 to promote and sustain macrophage polarization towards an anti-inflammatory phenotype. AU - Boehler, R. M.. AU - Kuo, R.. AU - Shin, S.. AU - Goodman, A. G.. AU - Pilecki, M. A.. AU - Leonard, J. N.. AU - Shea, L. D.. PY - 2014/6. Y1 - 2014/6. N2 - Gene delivery from biomaterials can create an environment that promotes and guides tissue formation. However, the immune response induced upon biomaterial implantation can be detrimental to tissue regeneration. Macrophages play a central role in mediating early phases of this response, and functional polarization of macrophages towards M1 (inflammatory) or M2 (anti-inflammatory) phenotypes may bias the local immune state at the implant site. Since gene delivery from biomaterial scaffolds can confer transgene expression in macrophages in vivo, we investigated whether transduction of macrophages with an IL-10 encoding lentivirus can (1) induce macrophage polarization toward an M2 phenotype even in an ...
Axol iPSC-Derived Macrophages are derived from iPSCs that have undergone an intermediate differentiation to monocytes prior to directed terminal differentiation to macrophages. This provides a highly pure and consistently reproducible population of macrophages. To support the growth and maintenance of Axol iPSC-Derived Macrophages, we offer a chemically defined, serum-free, fully optimized Macrophage Maintenance Medium.. One of the key functions of macrophages is to clean up! More specifically, by engulfing and destroying foreign substances, cell debris and microbes. Our iPSC-Derived Macrophages are highly phagocytic and express the ionized calcium-binding adapter molecule 1 (IBA1), which is typically expressed by macrophages upon activation.. When recruited to the site of injury and infection macrophages have the ability to differentiate to specific macrophage subtypes dependent on their location within the body. Within the lungs, pulmonary macrophages are a good example of tissue-specific ...
Macrophages are usually found in tumor infiltrates where they exert cytostatic/cytotoxic activities against tumor cells. The tumoricidal activity is enhanced by activation of macrophages with bacterial products or cytokines (1,2). Recently nitric oxide (NO) has been indicated as a critical effector molecule for macrophage anti-tumor activity (3,4). Macrophages can be induced to release NO upon stimulation with a variety of stimuli such as bacterial products or cytokines (3,5). More recently it has been reported that mycoplasma-treated macrophages release large amounts of NO (6).. YAC-1 tumor cells have been classically used as targets for natural killer (NK) cells. Resident macrophages do not present anti-YAC-1 activity, but lymphokine-activated macrophages are able to kill YAC-1 cells (7). The mechanism by which lymphokine-activated macrophages kill YAC-1 cells remains unsettled.. Based on these observations, we asked whether mycoplasma-infected YAC-1 tumor cells could stimulate macrophages to ...
TY - JOUR. T1 - Effect of SXWS/WSXWS peptides on chemotaxis and adhesion of the macrophage-like cell line J774. AU - Szabõ, Rita. AU - Láng, Orsolya. AU - Láng, Júlia. AU - Illyés, Eszter. AU - Köhidai, Lászlõ. AU - Hudecz, Ferenc. PY - 2015/4. Y1 - 2015/4. N2 - WSXWS motif is a conserved amino acid sequence that is present in type I cytokine receptors. This motif that can be found both in the ligand binding chains and signal transducer molecule of the receptors with different amino acids at the position X plays a role in the receptor folding, ligand binding and signal transduction as well. Structural analysis proved that WSEWS motif of IL-6R is located in a highly accessible location in the protein. Structural properties and chemotaxis of a tetrapeptide library with SXWS sequence, where X was the 19 proteinogenic amino acids except cystein were systematically studied earlier. It has been proved that C-terminal amidation and the identity of amino acid X had a pronounced influence on ...
Macrophage recognition of Candida albicans (C. albicans) is facilitated by pattern recognition receptors that interact with the fungal pathogen associated molecular patterns (PAMPs). Dectin-1 is the major macrophage receptor that is known to recognize fungal Beta-glucans leading to induction of various immune responses. This receptor is also known to be required for in vivo protection against C. albicans (Taylor et al., 2007). We recently showed that the Dectin-1 mediated protection in vivo is strain-dependent, and that C. albicans can adapt to modulate immune recognition by Dectin-1 (Marakalala et al., 2013). In vitro analysis, however, showed a Dectin-1-dependent and pro-inflammatory responses against all strains tested. This protocol describes in detail the in vitro analysis used in the paper. In particular, methods involved in fluorescent labeling of live C. albicans, quantification of macrophage binding of the pathogen, and pro-inflammatory responses to yeast and hyphal forms of the fungi are
Macrophages display remarkable plasticity, with the ability to undergo dynamic transition between different functional phenotypes.63,64 Macrophages activated by TLR ligands and IFN-γ are called M1 macrophages (also referred to as classically activated macrophages).63-65 Conversely, stimulation of macrophages with Th2 cytokines, such as IL-4 or IL-13, immune complexes plus TLR ligands, IL-10, transforming growth factor-β, or glucocorticoids induces the generation of M2-type macrophages (also called alternatively activated macrophages).63-65 M1 macrophages produce high amounts of proinflammatory cytokines and NO by expressing inducible NO synthase and are important for eradicating bacterial, viral, and fungal infections.63-65 M2 macrophages are characterized by their high expression of markers of alternative activation, such as arginase-1, Chitinase 3-like 3 (also called YM-1), and found in inflammatory zone 1 (FIZZ1), and regulate responses to parasite infection, tissue remodeling, ...
Tumor-associated macrophages (TAMs) have an ambiguous and complex role in the carcinogenic process, since these cells can be polarized into different phenotypes (proinflammatory, antitumor cells or anti-inflammatory, protumor cells) by the tumor microenvironment. Given that the interactions between tumor cells and TAMs involve several players, a better understanding of the function and regulation of TAMs is crucial to interfere with their differentiation in attempts to skew TAM polarization into cells with a proinflammatory antitumor phenotype. In this study, we investigated the modulation of macrophage tumoricidal activities by the lectin jacalin. Jacalin bound to macrophage surface and induced the expression and/or release of mainly proinflammatory cytokines via NF-|i|κ|/i|B signaling, as well as increased iNOS mRNA expression, suggesting that the lectin polarizes macrophages toward the antitumor phenotype. Therefore, tumoricidal activities of jacalin-stimulated macrophages were evaluated. High
Tumor-associated macrophages (TAMs) are the multifarious group of cells that originate mainly from the peritumoral tissue or bone marrow and can be divided into two main types: M1 and M2. Among them are the infiltrating M1 tumor-associated macrophages present in the early stages of tumorigenesis, which can secrete proinflammatory cytokines and in turn inhibit tumor growth. On the contrary, M2 tumor-associated macrophages are predominant in the late stage of tumor formation. Type II cytokines, which are secreted by them, can promote anti-inflammatory reaction and thus promote tumor growth. However, it remains unclear when M1 tumor-associated macrophages are transformed to M2 tumor-associated macrophages, but tumor hypoxia is currently thought to be associated with such a shift. M2 tumor-associated macrophages secrete many proteases such as cathepsin, cytokines, and an epidermal growth factor. The presence of M2 TAMs make the tumor prone to growth and angiogenesis, which in turn damages other ...
Soluble products from antigen stimulated Trypanosoma cruzi-immune spleen cells enhanced the expression of Ia antigens on proteose-peptone-elicited mouse peritoneal macrophages (M phi). Acquisition of Ia paralleled M phi activation, previously shown to be mediated by this same source of lymphokine (LK). Expression of Ia and four other plasma membrane antigens was monitored by quantitative binding and radioautographic studies with 125I-monoclonal antibodies. Immune LK selectively enhanced expression of Ia and, to a lesser extent, H-2D relative to control LK from antigen-stimulated noninfected spleen. The levels of three other non-major histocompatibility complex (MHC) antigens, including the trypsin-resistant Fc receptor, were similar in cells exposed to both sources of LK. As little as 1% immune LK induced one-half maximal expression of Ia. Kinetic studies revealed that much of the Ia on freshly explanted peritoneal M phi was lost during the 1st d of culture. In the continued presence of immune ...
TY - JOUR. T1 - Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. AU - Ziegler, H. K.. AU - Unanue, E. R.. PY - 1982/1/1. Y1 - 1982/1/1. N2 - This paper describes the effects of two lysosomotropic compounds, ammonia and chloroquine, on the interaction of mononuclear phagocytes with immune T cells. The uptake and ingestion of Listeria monocytogenes by macrophages were not affected by the drugs; however, the macrophage catabolism of 125I-labeled Listeria was reduced in a dose-dependent way. The macrophage presentation of Listeria to T cells, an I-region-dependent phenomenon, was also inhibited. The degree of inhibition of catabolism paralleled that of antigen presentation. The inhibition of antigen presentation took place if the macrophages were treated before and during Listeria uptake; minimal inhibition took place if the macrophages were treated 30 min after Listeria ingestion, at which time a ...
The engulfing, bactericidal and degrading activities toSalmonella typhi, strain ty2-4446 and 0-901 and toSalmonella enteritidis of guinea pig macrophages obtained from peritoneal exudate, spleen and bone marrow that were cultivated for 2-7 days, were studied. The phagocytic activity was expressed as a total number of phagocytosed microbes and the number of viable bacteria, released from mechanically disrupted macrophages. The ratio of phagocytosed bacteria to the original number of bacteria that were introduced to macrophage cultures, were evaluated in per cents. No significant difference in phagocytic activity was found between macrophages submitted to thein vitro cultivation and macrophages freshly isolated from the organism. Profound variations in phagocytic activity of cells were found which were partially dependent on the dose of microbes employed for the infection of cultures. Furthermore, both the engulfing and bactericidal activity of peritoneal macrophages toSalmonella typhi were found to be
TY - JOUR. T1 - Biochemical and genetic characterization of the multidrug resistance phenotype in murine macrophage-like J774.2 cells. AU - Kirschner, Lawrence S.. AU - Greenberger, Lee M.. AU - Hsu, Stephen I Hong. AU - Yang, Chia-Ping H.. AU - Cohen, Dalia. AU - Piekarz, Richard L.. AU - Castillo, Gonzalo. AU - Han, Edward Kyu Ho. AU - Yu, Lijia. AU - Band Horwitz, Susan. PY - 1992/1/9. Y1 - 1992/1/9. N2 - The development of multidrug resistance (MDR) in malignant tumors is a major obstacle to the treatment of many cancers. MDR sublines have been derived from the J774.2 mouse macrophage-like cell line and utilized to characterize the phenotype at the biochemical and genetic level. Two isoforms of the drug resistance-associated P-glycoprotein are present and distinguishable both electrophoretically and pharmacologically. Genetic analysis has revealed the presence of a three-member gene family; expression of two of these genes, mdr1a and mdr1b, is associated with MDR whereas the expression of ...
Human alveolar macrophages (AM) were obtained by bronchoalveolar lavage from 18 patients with a variety of conditions. For each patient the percentages of AM showing the following properties were determined: (1) staining for the enzymes non-specific esterase (NSE) and acid phosphatase (ACP); (2) in vitro phagocytosis of Candida guillermondii; (3) expression of cell surface markers detected by two monoclonal antibodies (MoAb) (1B5 and DA2) and two anti-monocyte/macrophage MoAb (UCHMI and RFD2); and (4) simultaneous phagocytosis of C. guillermondii and staining with the MoAb. In all patients the majority of AM were found to be Ia positive (90 +/- 10%) ACP positive (100%) and NSE positive (97 +/- 4%). In contrast a smaller proportion were UCHM1 and RFD2 positive (77 +/- 11%, 68 +/- 12%) and less were phagocytic (37 +/- 17%). Whilst the total percentage of cells staining with the MoAb was unaltered by phagocytosis, the proportion of UCHM1 or RFD2 positive cells was significantly higher in the phagocytic
Immortalized Murine Macrophage Cell Line as a Model for Macrophage Polarization into Classically Activated M(IFNγ+LPS) or Alternatively Activated M(IL-4) Macrophages Abstract.
Mammalian macrophages can adopt polarization states that, depending on the exact stimuli present in their extracellular environment, can lead to very different functions. Although these different polarization states have been shown primarily for macrophages of humans and mice, it is likely that polarized macrophages with corresponding phenotypes exist across mammals. Evidence of functional conservation in macrophages from teleost fish suggests that the same, or at least comparable polarization states should also be present in teleosts. However, corresponding transcriptional profiles of marker genes have not been reported thus far. In this study we confirm that macrophages from common carp can polarize into M1- and M2 phenotypes with conserved functions and corresponding transcriptional profiles compared to mammalian macrophages. Carp M1 macrophages show increased production of nitric oxide and a transcriptional profile with increased pro-inflammatory cytokines and mediators, including il6, il12 and saa.
In this report, we show that blockade of CSF1/CSF1R signaling in pancreatic tumors depletes CD206Hi TAMs and reprograms remaining macrophages to support antitumor immunity. The blockade alone modestly enhances antitumor IFN responses, promotes CTL infiltration, and slows tumor progression. However, the therapeutic effect is limited by the induction of T-cell checkpoint molecules, including PDL1 on tumor cells and CTLA4 on T cells. Addition of the CSF1/CSF1R blockade markedly improved the efficacy of αPD1 and αCTLA4 checkpoint immunotherapy and led to the regression of even well-established PDAC tumors. These data suggest that CSF1/CSF1R signaling may be an effective therapeutic target to reprogram the immunosuppressive microenvironment of human PDAC tumors and enhance the efficacy of immunotherapy.. Recent data from several groups suggest that inhibition of CSF1R signaling alters the immunologic responses of tumor-infiltrating macrophages in several cancer types (10-12, 31-33). Mok and ...
The atherosclerotic plaque is characterised by the presence of macrophage foam cells that arise from dysfunctional cholesterol metabolism and trafficking. Cytokines are highly expressed within the plaque and play a critical function in initiating and augmenting the disease state. Previous studies have shown that the novel cytokine, interleukin-33 (IL-33), exerts anti-atherogenic actions in animal and in vitro models of the disease. The effect of IL-33 on pro-atherosclerotic markers was assessed in human THP-1 and murine RAW264.7 macrophages and primary human monocyte-derived macrophages (HMDMs) by real time-quantitative polymerase chain reaction (RT-qPCR). The studies then focused on characterising the signalling pathways involved in the regulation of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemotactic protein-1 (MCP-1) expression by IL-33. The expression of key signalling components implicated in atherosclerosis were knocked down by RNA interference (RNAi). These experiments ...
The generation of T helper cells in vitro requires macrophages or macrophage-derived factors such as genetically related macrophage factor (GRF) or nonspecific macrophage factor (NMF). However, there is a basic difference of T helper cell induction when using particulate antigens. The present study demonstrates that this difference is based on the activation of two different T cell subsets. GRF activates short-lived T1 cells which amplify the induction of T2 cells, which are the helper cell precursors. Thus, the genetic restriction of T helper cell induction seen with soluble antigen or GRF lies on the level of macrophage or GRF interaction with T1 cells. NMF (or macrophages) and particulate antigens directly activate the helper cell precursor (T2) indicating no requirement for T1-T2 cooperation. The direct activation of the helper cell precursor with particulate antigens does not require histocompatible macrophages or NMF from histocompatible macrophages. The present results may explain some of the
Pharmacological interference with vacuolar-type H(+)-ATPase (V-ATPase), a proton-translocating enzyme involved in protein transport and pH regulation of cell organelles, is considered a potential strategy for cancer therapy. Macrophages are critically involved in tumor progression and may occur as pro-tumoral M2 phenotype, whereas classically-activated M1 can inhibit tumor development for example by releasing tumor-suppressing molecules, including tumor necrosis factor (TNF)alpha. Here, we show that targeting V-ATPase by selective inhibitors such as archazolid upregulates the expression and secretion of TNFalpha in lipopolysaccharide (LPS)- or LPS/interferon (INF)gamma-activated M1-like macrophages derived from human blood monocytes. In contrast, archazolid failed to elevate TNFalpha production from uncommitted (M0) or interleukin (IL)-4-treated M2-like macrophages. Secretion of other relevant cytokines (i.e., IL-1beta, IL-6, IL-10) or chemokines (i.e. IL-8 and monocyte chemotactic protein-1) ...
Tumour stromal macrophages differentiate to tumour-associated macrophages (TAMs) with characteristics of immunosuppressive M2-type macrophages, having a central role in promoting tumour vascularisation, cancer cell dissemination and in suppressing anti-cancer immune responses. Bisphosphonates (BPs) are a group of drugs commonly used as anti-resorptive agents. Further, nitrogen containing BPs like Zoledronate (ZOL), are known to cause unspecific inflammatory reactions hence the hypothesis that its use could modulate TAMs polarization toward a more inflammatory phenotype. We studied the in vitro polarization of J774 murine macrophages upon culture in 4T1 breast cancer cell-conditioned medium (4T1CM) and stimulation with LPS and free and liposome-encapsulated bisphosphonates. In this system, breast cancer soluble factors reduced the pro-inflammatory activation of macrophages but increased the secretion of matrix metalloproteinases (MMPs). In the presence of 4T1CM, a non-cytotoxic dose of liposome
View more ,The current RIKEN transcript set represents a significant proportion of the mouse transcriptome but transcripts expressed in the innate and acquired immune systems are poorly represented. In the present study we have assessed the complexity of the transcriptome expressed in mouse macrophages before and after treatment with lipopolysaccharide, a global regulator of macrophage gene expression, using existing RIKEN 19K arrays. By comparison to array profiles of other cells and tissues, we identify a large set of macrophage-enriched genes, many of which have obvious functions in endocytosis and phagocytosis. In addition, a significant number of LPS-inducible genes were identified. The data suggest that macrophages are a complex source of mRNA for transcriptome studies. To assess complexity and identify additional macrophage expressed genes, cDNA libraries were created from purified populations of macrophage and dendritic cells, a functionally related cell type. Sequence analysis revealed ...
The immediate tissue microenvironment of implanted biomedical devices and engineered tissues is highly influential on their long term fate and efficacy. The creation of a long-term anti-inflammatory microenvironment around implants and artificial tissues can facilitate their integration. Macrophages are highly plastic cells that define the tissue reactions on the implanted material. Local control of macrophage phenotype by long-term fixation of their healing activities and suppression of inflammatory reactions are required to improve implant acceptance. Herein, we describe the development of a cytokine cocktail (M2Ct) that induces stable M2-like macrophage phenotype with significantly decreased pro-inflammatory cytokine and increased anti-inflammatory cytokine secretion profile. The positive effect of the M2Ct was shown in an in vitro wound healing model; where M2Ct facilitated wound closure by human fibroblasts in co-culture conditions. Using a model for induction of inflammation by LPS we have ...
Macrophages were first identified by Elie Metchnikoff more than a century ago as cells essential for host defense. Despite the fact that macrophages are one of the oldest immune cells known to man, this field is currently undergoing a thrilling revival as recent technological advances have revealed the fascinating diversity of macrophages and their essential functions in tissue homeostasis, wound healing, morphogenesis, cancer and metabolism. Importantly, it is now clear that macrophages in inflamed tissues comprise distinct subsets that differ in cellular origin and functional specialization.. This complexity has forced researchers to develop new tools to study the role of these intriguing cells in health and disease. Technological advances now permit the transcriptomic profiling and precise tissue localization of macrophages at the single-cell level, but these advances also bring puzzling questions regarding the inter- and intracellular networks that control macrophage function.. To help meet ...
In our bitransgenic mouse model, we demonstrate that hypoxia provokes an accumulation of alternatively activated alveolar macrophages that precedes the development of pulmonary hypertension and appears to play a critical role in the pathogenesis of disease. Overexpression of HO-1 induced a switch in macrophage polarity toward an anti-inflammatory phenotype, and this effect was associated with protection from HPH.. Hypoxia resulted in alveolar inflammation that consisted predominantly of macrophages. These findings correlate with the fact that macrophages tend to accumulate in poorly vascularized areas with low oxygen tension,29 and correlates with previous studies in HPH that highlighted the predominant role of the monocyte/macrophage lineage in modulating vascular remodeling.8 Additionally, we found that hypoxia in vivo and in vitro polarized the population of alveolar macrophages toward the M2 phenotype. Hypoxic microenvironment is also a hallmark feature of tumors, and similar to the hypoxic ...
Results Natural anti-oxLDL IgM monoclonal antibody 3A6 specifically inhibited the binding of CuoxLDL to naïve macrophages in vitro. 3A6 failed to inhibit the binding of CuoxLDL to LPS-activated macrophages and promoted the formation of CuoxLDL-mediated foam macrophages. Furthermore, 3A6 F (ab′)2 or pre-incubation with un-related IgM inhibited the binding of 3A6/CuoxLDL complex to LPS-activated macrophages, suggesting that the Fcα/μ receptor may be responsible for the binding of 3A6/CuoxLDL complex to LPS-activated macrophages. Indeed, LPS up-regulated the expression of Fcα/μ receptor in macrophages in a dose- and time-dependent manner, which was diminished by treatment with anti-TLR4 neutralising mAb. In addition, LPS induced the phosphorylation of p38MAPK and translocation of NF-kB p65, contributing to the up-regulated expression of Fcα/μ receptor in macrophages as treatment with specific inhibitor for p38MAPK (SB203580) or NF-kB (PDTC) attenuated the up-regulation of Fca/m receptor ...
The interactions established between macrophages and cancer cells are largely dependent on instructions from the tumour microenvironment. Macrophages may differentiate into populations with distinct inflammatory profiles, but knowledge on their role on cancer cell activities is still very scarce. In this work, we investigated the influence of pro-inflammatory (LPS-stimulated) and anti-inflammatory (IL-10-stimulated) macrophages on gastric and colorectal cancer cell invasion, motility/migration, angiogenesis and proteolysis, and the associated molecular mechanisms. Following exposure of gastric and colon cancer cell lines to LPS- and IL-10-stimulated human macrophages, either by indirect contact or conditioned media, we analyzed the effect of the different macrophage populations on cancer cell invasion, migration, motility and phosphorylation status of EGFR and several interacting partners. Cancer-cell induced angiogenesis upon the influence of conditioned media from both macrophage populations was
M1 macrophages are more effective in the induction of the inflammatory response and clearance of Mycobacterium tuberculosis than M2 macrophages. Infected C57BL/6 mice generate a stronger cellular immune response compared with BALB/c mice. We hypothesized that infected C57BL/6 mice would exhibit a higher frequency and function of M1 macrophages than infected BALB/c mice. Our findings show a higher ratio of macrophages to M2 macrophages in the lungs of chronically infected C57BL/6 mice compared with BALB/c mice. However, there was no difference in the functional ability of M1 and M2 macrophages for the two strains in vitro. In vivo, a deleterious role for M2 macrophages was confirmed by M2 cell transfer, which rendered the infected C57BL/6, but not the BALB/c mice, more susceptible and resulted in mild lung inflammation compared with C57BL/6 mice that did not undergo cell transfer. M1 cell transfer induced a higher inflammatory response, although not protective, in infected BALB/c mice compared with their
Unkeless, J C., The presence of two fc receptors on mouse macrophages. Evidence from a variant cell line and differential trypsin sensitivity. (1977). Subject Strain Bibliography 1977. 2386 ...
macrophages; Bone Marrow-Derived Macrophages; Monocyte-Derived Macrophages. On-line free medical diagnosis assistant. Ranked list of possible diseases from either several symptoms or a full patient history. A similarity measure between symptoms and diseases is provided.
Macrophages are very important in the pathogenesis of rheumatoid arthritis (RA). The increase in the number of sublining macrophages in the synovium is an early hallmark of active rheumatic disease, and high numbers of macrophages are a prominent feature of inflammatory lesions. The degree of synovi …
Our recent findings lay the groundwork for new cellular therapy approaches in regenerative medicine. One important line of our work has revealed mechanisms how hematopoietic stem cells can generate more myeloid cells, including macrophages, to protect transplant recipients from lethal infections. Furthermore, we discovered that macrophages, mature cells of the immune system, could activate a network of self-renewal genes shared with embryonic stem cells that enables them to proliferate indefinitely. This makes it possible to amplify macrophages in culture as mature differentiated cells, without stem cell intermediates or tumorigenic transformation. Our results show that not only stem cells but also mature cells like macrophages can activate self-renewal mechanisms. This opens the door for new macrophage-based therapies.. ...
Using a mouse model of spinal injury, Michal Schwartz and colleagues tested the effect of macrophages on the recovery process and demonstrate an important anti-inflammatory role for a subset of infiltrating monocyte-derived macrophages that is dependent upon their expression of interleukin 10.
Polarization has been a useful concept for describing activated macrophage phenotypes and gene expression profiles. However, macrophage activation status within tumors and other settings are often inferred based on only a few markers. Complicating matters for relevance to human biology, many macrophage activation markers have been best characterized in mice and sometimes are not similarly regulated in human macrophages. To identify novel markers of activated human macrophages, gene expression profiles for human macrophages of a single donor subjected to 33 distinct activating conditions were obtained and a set of putative activation markers were subsequently evaluated in macrophages from multiple donors using integrated fluidic circuit (IFC)-based RT-PCR. Using unsupervised hierarchical clustering of the microarray screen, highly altered transcripts (>4-fold change in expression) sorted the macrophage transcription profiles into two major and 13 minor clusters. Among the 1874 highly altered transcripts,
Looking for online definition of macrophage/monocyte inhibitory factor in the Medical Dictionary? macrophage/monocyte inhibitory factor explanation free. What is macrophage/monocyte inhibitory factor? Meaning of macrophage/monocyte inhibitory factor medical term. What does macrophage/monocyte inhibitory factor mean?
The cellular mechanisms which account for the formation of osteoclasts and bone resorption associated with enlarging benign and malignant mesenchymal tumours of bone are uncertain. Osteoclasts are marrow-derived, multinucleated, bone-resorbing cells which express a macrophage phenotype. We have determined whether tumour-associated macrophages (TAMs) isolated from benign and malignant mesenchymal tumours are capable of differentiating into osteoclasts. Macrophages were cultured on both coverslips and dentine slices for up to 21 days with UMR 106 osteoblastic cells in the presence of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) and human macrophage colony-stimulating factor (M-CSF) or, in the absence of UMR 106 cells, with M-CSF and RANK ligand. In all tumours, the formation of osteoclasts from CD14-positive macrophages was shown by the formation of tartrate-resistant-acid-phosphatase and vitronectin-receptor-positive multinucleated cells which were capable of carrying out lacunar resorption. These results
TY - JOUR. T1 - Increased muscle proteolysis after local trauma mainly reflects macrophage-associated lysosomal proteolysis. AU - Farges, M C AU - Balcerzak, Denis Pierre. AU - Fisher, B D AU - Attaix, D AU - Bechet, D AU - Ferrara, M AU - Baracos, V E PY - 2002/2. Y1 - 2002/2. N2 - Rat gastrocnemius showed increased protein degradation (+75-115%) at 48 h after traumatic injury. Injured muscle showed increased cathepsin B activity (+327%) and mRNA encoding cathepsin B (+670%), cathepsin L (+298%), cathepsin H (+159%), and cathepsin C (+268%). In in situ hybridization, cathepsin B mRNA localized to the mononuclear cell infiltrate in injured muscle, and only background levels of hybridization were observed either over muscle cells in injured tissue or in uninjured muscle. Immunogold/electron microscopy showed specific staining for cathepsin B only in lysosome-like structures in cells of the mononuclear cell infiltrate in injured muscle. Muscle cells were uniformly negative in the ...
TY - JOUR. T1 - Liver macrophage-associated inflammation correlates with SIV burden and is substantially reduced following cART. AU - Fisher, Bridget S.. AU - Green, Richard R.. AU - Brown, Rachel R.. AU - Wood, Matthew P.. AU - Hensley-McBain, Tiffany. AU - Fisher, Cole. AU - Chang, Jean. AU - Miller, Andrew D.. AU - Bosche, William J.. AU - Lifson, Jeffrey D.. AU - Mavigner, Maud. AU - Miller, Charlene J.. AU - Gale, Michael. AU - Silvestri, Guido. AU - Chahroudi, Ann. AU - Klatt, Nichole R.. AU - Sodora, Donald L.. N1 - Funding Information: This project was supported by funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health grant R21AI100782 (DLS) ( and funds from the National Institute of Dental and Craniofacial Research, National Institutes of Health grant R01DE023047 (DLS) ( Research was also supported in part with Federal funds from the National Institute of Allergy and Infectious Diseases, ...
TY - JOUR. T1 - Expression of Gα(i2) mimics several aspects of LPS priming in a murine macrophage-like cell line. AU - Kugi, M.. AU - Kitamura, K.. AU - Cottam, G. L.. AU - Miller, R. T.. PY - 1995/1/1. Y1 - 1995/1/1. N2 - Priming of macrophages with low concentrations of lipopolysaccharide (LPS) enhances the ability of substances that act through heterotrimeric G proteins to stimulate immune cell functions. Although LPS-induced alterations in the expression and functions of G proteins of the α(i) family have been reported in hematopoietic cells, their effects on subsequent steps in LPS priming of macrophages have not been defined. To study the role of Gα(i2) in priming of macrophages by LPS, we expressed a mutant, activated form of α(i2) (α(i2Q2051)) in P388D1 cells, and compared its effects on PAF-dependent Ca signalling and arachidonic acid release to those in cells treated with LPS. In control P388D1 cells, treatment with LPS (100 ng/ml) for 1 hr increased the amount of α(i2) protein ...
TY - JOUR. T1 - Differential mRNA expression of prostaglandin receptor subtypes in macrophage activation. AU - Hubbard, Neil. AU - Lee, S. H.. AU - Lim, D.. AU - Erickson, Kent L. PY - 2001. Y1 - 2001. N2 - Assessing the regulation of macrophage receptors for prostaglandin (PGE2) is essential to understanding the control which that potent lipid mediator has in modulating macrophage activities. The purpose of this study was to assess the differential mRNA expression of PGE2 receptor subtypes (EP) during macrophage exposure to activating and transducing agents. RAW 264.7 macrophages constitutively expressed mRNA for EP2, EP3 and EP4 receptor subtypes. Messenger RNA for EP4 was expressed at a much higher level when compared to EP2 in unstimulated macrophages as assessed by kinetic quantitative RT-PCR. When macrophages were stimulated with LPS, EP2 mRNA levels were 12-fold higher when compared to unstimulated macrophages, while EP4 mRNA remained unchanged. Conversely, mRNA levels of both EP2 and EP4 ...
TY - JOUR. T1 - HIV-1 inhibits phagocytosis and inflammatory cytokine responses of human monocyte-derived macrophages to P. falciparum infected erythrocytes. AU - Ludlow, Louise E. AU - Zhou, Jingling. AU - Tippett, Emma Dawn. AU - Cheng, Wan-Jung. AU - Hasang, Wina. AU - Rogerson, Stephen J. AU - Jaworowski, Anthony. PY - 2012. Y1 - 2012. N2 - HIV-1 infection increases the risk and severity of malaria by poorly defined mechanisms. We investigated the effect of HIV-1(Ba-L) infection of monocyte-derived macrophages (MDM) on phagocytosis of opsonised P. falciparum infected erythrocytes (IE) and subsequent proinflammatory cytokine secretion. Compared to mock-infected MDM, HIV-1 infection significantly inhibited phagocytosis of IE (median (IQR) (10 (0-28) versus (34 (27-108); IE internalised/100 MDM; p = 0.001) and decreased secretion of IL-6 (1,116 (352-3,387) versus 1,552 (889-6,331); pg/mL; p = 0.0078) and IL-1beta (16 (7-21) versus 33 (27-65); pg/mL; p = 0.0078). Thus inadequate phagocytosis and ...
Cellular proliferation and macrophage influx precede interstitial fibrosis in cyclosporine nephrotoxicity is an eagle-i resource of type Journal article at eagle-i Network Shared Resource Repository.
TY - JOUR. T1 - Elevated A20 contributes to age-dependent macrophage dysfunction in the lungs. AU - Hinojosa, Cecilia A.. AU - Akula Suresh Babu, Ramya. AU - Rahman, Md M.. AU - Fernandes, Gabriel. AU - Boyd, Angela R.. AU - Orihuela, Carlos J.. N1 - Funding Information: We thank David E. Harrison and Kevin Flurkey at The Jackson Laboratory for their gift of aged mice. Financial support for CJO came from the Morrison Trust , The Glenn Foundation , and NIH AG033274 . Copyright: Copyright 2014 Elsevier B.V., All rights reserved.. PY - 2014/6. Y1 - 2014/6. N2 - Advanced age is associated with chronic low-grade inflammation (i.e. inflamm-aging) and poor macrophage function that includes a weak pro-inflammatory cytokine response to bacteria and diminished phagocytosis (i.e. age-dependent macrophage dysfunction [ADMD]). One reason for this is that ADMD is associated with poor NFκB and MAPK activation following Toll-like receptor stimulation. Herein, we tested the hypothesis that inflamm-aging induces ...
ER stress occurs in macrophage-rich areas of advanced atherosclerotic lesions and contributes to macrophage apoptosis and subsequent plaque necrosis. Therefore, signaling pathways that alter ER stressinduced apoptosis may affect advanced atherosclerosis. Here we placed Apoe/ mice deficient in macrophage p38α MAPK on a Western diet and found that they had a marked increase in macrophage apoptosis and plaque necrosis. The macrophage p38αdeficient lesions also exhibited a significant reduction in collagen content and a marked thinning of the fibrous cap, which suggests that plaque progression was advanced in these mice. Consistent with our in vivo data, we found that ER stressinduced apoptosis in cultured primary mouse macrophages was markedly accelerated under conditions of p38 inhibition. Pharmacological inhibition or genetic ablation of p38 suppressed activation of Akt in cultured macrophages and in atherosclerotic lesions. In addition, inhibition of Akt enhanced ER stressinduced macrophage ...
Upregulation of macrophage plasma membrane and nuclear phospholipase D activity on ligation of the alpha2-macroglobulin signaling receptor: involvement of heterotrimeric and monomeric G proteins.
The results of this study show that changes in numbers of synovial sublining macrophages correlate with clinical improvement independently of the therapeutic strategy. Furthermore, this study demonstrates that the change in the numbers of sublining macrophages may be used to explain clinical outcome. Of importance, the data indicate that the change in the number of sublining macrophages could be used as a sensitive biomarker to predict possible efficacy of a new antirheumatic treatment.. Previous work suggested an association between the number of synovial macrophages and joint destruction in RA.14 Moreover, analysis of the synovial cell infiltrate demonstrated a positive correlation between scores for local disease activity and the number of macrophages as well as expression of macrophage derived cytokines (tumour necrosis factor α (TNFα) and interleukin (IL) 6) in rheumatoid ST, suggesting that macrophage numbers are associated with clinical signs of inflammation.2 In keeping with this ...
In the human disorder multiple sclerosis (MS) and in the model experimental autoimmune encephalomyelitis (EAE), macrophages predominate in demyelinated areas and their numbers correlate to tissue damage. Macrophages may be derived from infiltrating monocytes or resident microglia, yet are indistinguishable by light microscopy and surface phenotype. It is axiomatic that T cell-mediated macrophage activation is critical for inflammatory demyelination in EAE, yet the precise details by which tissue injury takes place remain poorly understood. In the present study, we addressed the cellular basis of autoimmune demyelination by discriminating microglial versus monocyte origins of effector macrophages. We show that monocyte-derived macrophages associate with nodes of Ranvier and initiate demyelination, whereas microglia appear to clear debris. Gene expression profiles confirm that monocyte-derived macrophages are highly phagocytic and inflammatory, whereas those arising from microglia demonstrate an ...
Mechanical stress has been recognized as a key inducer of bone regeneration in bone damage, which is experimentally mimicked by distraction osteogenesis (DO), a bone-regenerative process induced by post-osteotomy distraction of the surrounding vascularized bone segments, and realized by new bone formation within the distraction gap. The mechanisms that underlie the DO-induced bone regeneration remain poorly understood and a role of macrophages in the process has been inadequately studied. Here, in a mouse model of DO, we showed significant increase in macrophages in the regeneration area. Moreover, in a loss-of-function approach by depleting inflammatory macrophages, the bone regeneration was compromised by assessment of histology and molecular biology. Thus, our study demonstrates the necessary participation of inflammatory macrophages in the process of DO-induced bone regeneration, and suggests that targeting inflammatory macrophages may help to improve clinical bone repair.
Introduction: Macrophages comprise an essential component of the mammary microenvironment necessary for normal gland development. However, there is no viable in vivo model to study their role in normal human breast function. We hypothesized that adding primary human macrophages to the murine mammary gland would enhance and provide a novel approach to examine immune-stromal cell interactions during the humanization process. Methods: Primary human macrophages, in the presence or absence of ectopic estrogen stimulation, were used to humanize mouse mammary glands.
In both cells and animals, cannibalism can transfer harmful substances from the consumed to the consumer. Macrophages are immune cells that consume their own dead via a process called cannibalistic efferocytosis. Macrophages that contain harmful substances are found at sites of chronic inflammation, yet the role of cannibalism in this context remains unexplored. Here we take mathematical and experimental approaches to study the relationship between cannibalistic efferocytosis and substance accumulation in macrophages. Through mathematical modelling, we deduce that substances which transfer between individuals through cannibalism will concentrate inside the population via a coalescence process. This prediction was confirmed for macrophage populations inside a closed system. We used image analysis of whole slide photomicrographs to measure both latex microbead and neutral lipid accumulation inside murine bone marrow-derived macrophages (104-[Formula: see text]) following their stimulation into an
The present study affirms our hypothesis that the Notch pathway plays an important role in macrophages, a key cell type in inflammation and atherosclerosis. Evidence that supports this idea includes the expression of multiple Notch receptors and ligands in human macrophages; markedly increased Dll4 expression in human macrophages stimulated with LPS, mmLDL, or IL-1β, an event that likely involves TLR4 and NF-κB; the ability of Dll4 to bind to macrophages and trigger Notch signaling; the induction of the MAPK, Akt, and NF-κB pathways in macrophages stimulated with Dll4; the Dll4-induced transcription of iNOS, PTX3, Id1, and Dll4 itself; and the presence of Notch pathway components, such as Dll4 and Notch3, in human atherosclerotic plaques rich in macrophages.. Dll4 expression induced in human primary macrophages by proinflammatory stimuli (LPS, IL-1β, and mmLDL) (Figures 2 through 4⇑⇑) and the detection of immunoreactive Dll4 in human atherosclerotic plaques (Figure 8) indicate possible ...
BioAssay record AID 309254 submitted by ChEMBL: Reduction of Mycobacterium tuberculosis H37Rv growth in mouse peritoneal macrophage monolayers after 7 days.
Macrophages are found in most tissues of the body, where they have tissue- and context-dependent roles in maintaining homeostasis as well as coordinating adaptive responses to a variety of stresses. Their capacity for specialized functions is controlled by polarizing signals, which activate (or polarize) macrophages by upregulating transcriptional programs that encode distinct effector functions. An important conceptual advance in the field of macrophage biology, emerging from recent studies, is that macrophage activation is critically supported by metabolic shifts. Metabolic shifts fuel multiple aspects of macrophage activation, and preventing these shifts impairs appropriate activation. These findings raise the exciting possibility that macrophage functions in various contexts could be regulated by manipulating their metabolism. Here we review the rapidly evolving field of macrophage metabolism, discussing how polarizing signals trigger metabolic shifts and how these shifts enable appropriate
Stewart, J; Glass, E J.; and Weir, D M., Macrophage binding of staphylococcus albus is blocked by anti i-region alloantibody. (1982). Subject Strain Bibliography 1982. 4410 ...
TY - JOUR. T1 - Niacin modulates macrophage polarization in Parkinsons disease. AU - Wakade, Chandramohan G.. AU - Giri, Banabihari. AU - Malik, Aneeq. AU - Khodadadi, Hesam. AU - Morgan, John Christopher. AU - Chong, Kwong Yew Raymond. AU - Baban, Babak. PY - 2018/7/15. Y1 - 2018/7/15. N2 - Neuroinflammation remains a central piece in Parkinsons disease (PD) pathophysiology. However, mechanisms by which PD links to the neuroinflammation remain elusive. Here, for the first time, we report that lower dose of niacin in PD patients may affect macrophage polarization from M1 (pro-inflammatory) to M2 (counter-inflammatory) profile through the niacin receptor GPR109A. Skew in the peripheral macrophages were accompanied by improved quality of life assessments in patients. Low dose niacin supplementation may be beneficial in PD, boosting anti-inflammatory processes and suppressing inflammation. Varied niacin dosages for longer durations may further reveal the potential role of anti-inflammatory ...
Intestinal macrophages, unlike macrophages from other tissues, do not support HIV-1 infection or produce proinflammatory cytokines. In vitro studies suggest this unique, functional phenotype is a result of the exposure of newly recruited blood monocytes to intestinal stromal products. However, in AIDS-related CMV colitis, mucosal macrophages express HIV-1 and proinflammatory cytokines. Therefore, we investigated the mechanism by which CMV confers permissiveness to HIV-1 and cytokine production on intestinal macrophages. We show that intestinal stroma-conditioned media (S-CM) down-regulated monocyte-derived macrophage infection by HIV-1 (pseudotyped with YU2 envelope or vesicular stomatitis virus glycoprotein) and production of TNF-α, but preinfection of the cells with CMV reversed this down-regulation, enhancing HIV-1 infection, p24 production, and TNF-α release. The ability of CMV to reverse S-CM down-regulation of macrophage HIV-1 infection was blocked by anti-TNF-α antibodies and ...
Inflammation plays a prominent role in atherosclerosis development and associated cardiovascular disease. Macrophages are key immune cells found in atherosclerotic plaques and critically shape atherosclerotic disease development and clinical outcome. They are one of the most plastic cells of the hematopoietic system. In response to micro-environmental stimuli they adopt different polarization states driving their functional repertoire in tissue homeostasis, host defense and pathology. Whilst several efforts have been made to classify macrophages, the binary M1/M2 classification remains the most used and offers a useful reductionist framework to study and describe their function.. We described the association of macrophage subsets with specific regions in human atherosclerotic plaques. Inflammatory M1 macrophages associated with plaque rupture prone shoulder regions, while M2 macrophages dominated in the adventitia. A main focus of our research interest is on the targeting of macrophage ...
Interferon gamma (IFN-γ) and leukemia inhibitory factor (LIF) are key gestational factors that may differentially affect leukocyte function during gestation. Because IFN-γ induces a pro-inflammatory phenotype in macrophages and because trophoblast cells are principal targets of LIF in the placenta, we investigated whether and how soluble factors from trophoblast cells regulate the effects of IFN-γ on macrophage activation. IFN-γ reduces macrophage motility, but enhances Stat1 activation, pro-inflammatory gene expression and cytotoxic functions. Soluble factors from villous cytotrophoblasts (vCT+LIF cells) and BeWo cells (BW/ST+LIF cells) that were differentiated in the presence of LIF inhibit macrophage Stat1 activation but inversely sustain Stat3 activation in response to IFN-γ. vCT+LIF cells produce soluble factors that induce Stat3 activation; this effect is partially abrogated in the presence of neutralizing anti-interleukin 10 (IL-10) antibodies. Moreover, soluble factors from BW/ST+LIF cells
TY - JOUR. T1 - Regulation of mannose receptor synthesis and turnover in mouse J774 macrophages. AU - Fiani, Maria L.. AU - Beitz, Jill. AU - Turvy, Diane. AU - Blum, Janice S.. AU - Stahl, Philip D.. PY - 1998/7. Y1 - 1998/7. N2 - The mannose receptor, present on the plasma membrane of macrophages, promotes the internalization of glycoproteins and glycoconjugates via both endocytic and phagocytic pathways. The expression of this receptor is tightly modulated during monocyte/MΦ differentiation and cellular activation. We isolated clonal populations from murine J774 macrophage tumor cells, which differ in their surface expression of functional mannose receptors. To examine the potential mechanisms regulating receptor function in these cell lines, the interaction of receptor with ligand as well as receptor synthesis and degradation was analyzed. J774 clones with both high and low levels of mannose receptor activity were found to synthesize significant amounts of receptor protein, suggesting that ...
Purpose: The mechanism by which alveolar macrophages increase in patients with chronic obstructive pulmonary disease (COPD) is still unknown. CD163, CD204 and CD206 are known to be markers of M2 macrophages, which are a specific macrophage phenotype. We investigated the expression of CD163, CD204 and CD206 on alveolar macrophages in COPD patients.. Methods: Immunohistochemical techniques were used to examine CD163, CD204 and CD206 expression on alveolar macrophages in the lungs of COPD patients, smokers and non-smokers.. Results: The numbers of alveolar macrophages in COPD patients were significantly greater in smoked and non-smokers. The numbers and percentages of CD163+, CD204+ or CD206+ alveolar macrophages in patients with COPD at GOLD stages III and IV were significantly higher than in those at GOLD stages I and II, and those in smokers and non-smokers.. Conclusion: Overproduction of CD163, CD204 and CD206 on alveolar macrophages in the lungs may be involved in the pathogenesis of COPD. ...
Alveolar tissue macrophage phagocytosis of E. coli, scanning electron micrograph (SEM). Note the macrophage has short filopodia that extend from the cell and aid in finding bacteria for phagocytosis. A tissue macrophage is a large, mature phagocyte that can ingest and destroy invading microbes, foreign particles, cancerous or diseased cells and cellular debris. Alveolar (lung pleural cavity) macrophages are part of the reticuloendothelial system. Magnification: x800 when shortest axis printed at 25 millimetres. - Stock Image C036/9773
Phagocytic cells are a critical line of defense against infection. The ability of a pathogen to survive and even replicate within phagocytic cells is a potent method of evading the defense mechanisms of the host. A number of pathogens survive within macrophages after phagocytosis and this contributes to their virulence. Salmonella is one of these pathogens. Here we report that 6-14 hr after Salmonella enters the macrophage and replicates, it resides in large vacuoles and causes the destruction of these cells. Furthermore, we identified four independently isolated MudJ-lacZ insertion mutants that no longer cause the formation of these vacuoles or kill the macrophages. All four insertions were located in the ompR/envZ regulon. These findings suggest that killing and escape from macrophages may be as important steps in Salmonella pathogenesis as are survival and replication in these host cells.. ...
The role of macrophages in the pathogenesis of lupus nephritis, in particular their differentiation to a certain subtype (e.g., M1- or M2-like) modulating the inflammatory reaction, is unknown. Here we investigated whether the differentiation in M1- or M2-like macrophages depends on the stage of lupus nephritis and whether this correlates with clinical parameters. Using immunohistochemical analysis we analyzed renal biopsies from 68 patients with lupus nephritis (ISN/RPS classes II-V) for infiltration with M1-like (iNOS+/CD68+), M2a-like (CD206+/CD68+), M2c-like macrophages (CD163+/CD68+), and FoxP3+ regulatory T-cells. In addition, clinical parameters at the time of renal biopsy, i.e., blood pressure, proteinuria and serum urea were correlated with the macrophage infiltration using the Spearman test. The mean number of CD68+ macrophages was related to the diagnosed ISN/RPS class, showing the highest macrophage infiltration in biopsies with diffuse class IV and the lowest number in ISN/RPS class V. In
TY - JOUR. T1 - Human lung macrophages enhance and inhibit lymphocyte proliferation. AU - Liu, M. C.. AU - Proud, D.. AU - Schleimer, R. P.. AU - Plaut, M.. PY - 1984/1/1. Y1 - 1984/1/1. N2 - To evaluate the effector functions of human lung macrophages, cell preparations containing 70 to 95% macrophages were obtained from surgically resected lungs of cancer patients and were co-cultured with allogeneic or autologous peripheral blood mononuclear cells (PBMC) and Con A. In contrast to previous reports of either marked stimulatory or inhibitory effects of human lung macrophages on lymphocyte function, the present results demonstrate that the proliferative response was a complex function of both the numbers of PBMC and macrophages. In the presence of low numbers of PBMC, small numbers of macrophages enhanced proliferation, whereas larger numbers inhibited proliferation; in the presence of larger numbers of PBMC, macrophages only inhibited. Inhibition was not mediated by cyclo-oxygenase products of ...
This is the first study to demonstrate distinct correlation of alveolar macrophage dysfunction with clinical predilection towards COPD exacerbations. Furthermore, this association occurred in response to NTHI, M catarrhalis, and S pneumoniae, the three most common respiratory pathogens in COPD.19 An evoked alveolar macrophage inflammatory response is critical for innate immune-mediated bacterial clearance. Occurrence of bacterial exacerbations is primarily driven by acquisition of new bacterial pathogens in the lower respiratory tract.2 Increased lower airway inflammation has been linked to increased respiratory symptoms in COPD leading to clinical exacerbations.20 With the introduction of new strains of respiratory pathogens and impaired macrophage clearance, bacteria persist. Failure to clear respiratory bacteria may promote exacerbations and require adaptive immune mechanisms for pathogen clearance.. We previously discovered that alveolar macrophages of adults with COPD had impaired ...
About 6 million Americans suffer from heart failure and 70% of heart failure cases are caused by myocardial infarction (MI). Following myocardial infarction, increased cytokines induce two major types of macrophages: classically activated macrophages which contribute to extracellular matrix destruction and alternatively activated macrophages which contribute to extracellular matrix construction. Though experimental results have shown the transitions between these two types of macrophages, little is known about the dynamic progression of macrophages activation. Therefore, the objective of this study is to analyze macrophage activation patterns post-MI. We have collected experimental data from adult C57 mice and built a framework to represent the regulatory relationships among cytokines and macrophages. A set of differential equations were established to characterize the regulatory relationships for macrophage activation in the left ventricle post-MI based on the physical chemistry laws. We further
Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers in the human population. HCC is an inflammation-associated cancer caused by different etiological factors. The chronic inflammation leads to continuous cycles of hepatocytes destructive-regenerative process and contributes to HCC initiation and progression. Macrophages play a crucial role in chronic liver inflammation. The tumor microenvironment plays a key role in the progression of HCC. Tumor-associated macrophages are a well-known component of the tumor microenvironment and abundantly infiltrate HCC microenvironment. The roles of macrophages in the development and progression of HCC have been recognized. The deep understanding of macrophages in HCC will be critical for developing effective HCC therapy. Targeting of macrophages might provide novel therapeutic approaches for HCC patients and is an emerging field of interest. This review summarizes the knowledge on the contribution of macrophages in the development and
TY - JOUR. T1 - Recruitment of exogenous macrophages into metastases at different stages of tumor growth. AU - Bugelski, Peter J.. AU - Kirsh, Richard. AU - Buscarino, Charles. AU - Corwin, Steven P.. AU - Poste, George. PY - 1987/4/1. Y1 - 1987/4/1. N2 - The endogenous tumor-associated macrophage content and recruitment of labeled peritoneal exudate cells into experimental murine B16 melanoma metastases has been examined at different stages in the progressive growth of metastatic lesions. The recruitment of thioglycollate-elicited peritoneal exudate cells and peritoneal exudate cells activated in vitro with muramyl dipeptide was studied. Tumor-associated macrophages and labeled peritoneal exudate cells were identified in paraffin sections by specific histochemical staining and their density in individual metastases measured morphometrically. The density of tumor-associated macrophages and exogenously recruited peritoneal exudate cells was high in very small lesions but decreased rapidly as a ...
Aging is closely associated with atherosclerosis. Macrophages accumulate in atherosclerotic lesions contributing to the development and progression of atherosclerosis. Although atherosclerotic lesions are known to contain senescent cells, the mechanism underlying the formation of senescent macrophages during atherosclerosis is still unclear. In this study, macrophages with different origins were collected, including THP-1 macrophages, telomerase reverse transcriptase knock out (Tert-/-) mouse peritoneal macrophages, and human peripheral blood mononuclear cells (PBMCs). We found Lipopolysaccharide (LPS) could induce the formation of senescent macrophages, which was typified by the morphological changes, senescence-associated secretory phenotype (SASP) secretory, and persistent DNA damage response. Mechanistically, bromodomain-containing protein 4 (BRD4), a chromosomal binding protein related to gene expression, was found to play a key role in the pathological process, which could offer new
Gamma-glutamyltransferase (GGT) is a well-established independent risk factor for cardiovascular mortality related to atherosclerotic disease. Four GGT fractions have been identified in plasma, but only b-GGT fraction accumulates in atherosclerotic plaques, and correlates with other histological markers of vulnerability. The present study was aimed to evaluate whether macrophagic lineage cells may provide a source of b-GGT within the atherosclerotic plaque. GGT expression and release were studied in human monocytes isolated from peripheral blood of healthy donors. The growth factors GM-CSF and M-CSF were used to induce differentiation into M1-like and M2-like macrophages, respectively. Plaque GGT was investigated in tissue samples obtained from patients undergoing carotid endoarterectomy. We found that M1-like macrophages express higher levels of GGT as compared to M2-like, and that both monocytes and M1-like macrophages-but not M2-like-are able to release the b-GGT fraction upon activation with pro
Intestinal Macrophages in Resolving Inflammation. Ashley M. Hine and Png Loke. J Immunol August 1, 2019, 203 (3) 593-599; DOI ... Intestinal Macrophages in Resolving Inflammation Message Subject (Your Name) has forwarded a page to you from The Journal of ... Hence, macrophages are intriguing targets for immune-mediated therapies, especially when barrier function in the gut is ... Macrophages not only regulate intestinal homeostasis by recognizing pathogens to control enteric infections but also employ ...
  • Macrophages primarily originate from circulating monocytes and resident tissues. (
  • Granulocyte/macrophage progenitors (GMPs), for example, are clonogenic bone marrow cells that descend from HSCs and commit to either neutrophils or monocytes. (
  • Circulating monocytes become tissue macrophages (or dendritic cells), whereas circulating neutrophils become activated tissue neutrophils. (
  • Macrophages develop from circulating monocytes that migrate from the blood into tissues throughout the body, especially the spleen, liver, lymph nodes, lungs, brain, and connective tissue. (
  • Macrophages are formed through differentiation of monocytes, one of the major groups of white blood cells of the immune system. (
  • When there is tissue damage or infection, the monocytes leave the blood stream and enter the affected tissue or organ and undergo a series of changes to become macrophages. (
  • Synovial macrophages are one of the resident cell types in synovial tissue and while they remain relatively quiescent in the healthy joint, they become activated in the inflamed joint and, along with infiltrating monocytes/macrophages, regulate secretion of pro-inflammatory cytokines and enzymes involved in driving the inflammatory response and joint destruction. (
  • Macrophage is any of the specialized class of large, phagocytic cells within the tissues , including blood , that originate from specific white blood cells called monocytes and that destroy foreign bacteria and other microorganisms as well as cellular debris, and senescent and damaged cells. (
  • Macrophages are thought to mature continuously from circulating monocytes. (
  • The three main categories of leukocytes are granulocytes (neutrophils, basophils, eosinophils), lymphocytes ( B cells , T cells , natural killer cells), and monocytes (including macrophages). (
  • Human macrophages are about 21 micrometres (0.00083 in) in diameter [5] and are produced by the differentiation of monocytes in tissues. (
  • Macrophages that reside in adult healthy tissues either derive from circulating monocytes or are established before birth and then maintained during adult life independently of monocytes. (
  • Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. (
  • Macrophages are highly plastic leukocytes that differentiate from monocytes following their entry into extravascular tissues. (
  • Once monocytes reach the arterial wall intima, they undergo phenotypic transformation into macrophages, internalise large amounts of modified LDLs and become foam cells. (
  • Monocytes transmigrate to the subendothelial space, where they transform into macrophages and begin producing enzymes that oxidatively modify LDL, such as 12/15‐LO and enzymes that produce ROS. (
  • Additionally, bone marrow-derived monocytes give rise to macrophages in the intestine and the dermis ( 6 , 7 ), as well as during acute infection and inflammation ( 8 ). (
  • Populations II and III phenotypically resembled Ly6C + inflammatory monocytes and neutrophils, respectively, while population I expressed classical dendritic cell (DC) markers MHCII and CD11c and the macrophage marker F4/80. (
  • Macrophages [1] are white blood cells within tissues, produced by the differentiation of monocytes . (
  • Monocytes and macrophages are phagocytes , acting in general immunity . (
  • This antibody is reactive to the majority of mouse monocytes and a subset of mature resident macrophages, especially those located in hemopoietic organs. (
  • In the tissues monocytes mature into different types of macrophages at different anatomical locations. (
  • Airway macrophages are derived from recipient circulating monocytes after transplant. (
  • Recent murine studies suggest that resident pulmonary macrophages self-maintain locally, with minimal contribution from circulating monocytes during health. (
  • Since monocytes are known macrophage precursors, the authors questioned next the origin of AMs in the human lung. (
  • Monocytes, macrophages and foam cells are the central players in atherosclerosis and contribute to all stages of lesion formation. (
  • Skewing monocytes and macrophages to cells with anti-atherogenic properties could be envisaged as an athero-protective treatment. (
  • The overall aim of this thesis was to identify novel regulators in monocytes and macrophages to combat atherosclerosis. (
  • Monocytes and macrophages are phagocytes, acting in both non-specific defense (or innate immunity) as well as to help initiate specific defense mechanisms (or adaptive immunity) of vertebrate animals. (
  • 2014) Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. (
  • Ginhoux F and Jung S (2014) Monocytes and macrophages: developmental pathways and tissue homeostasis. (
  • Chronic inflammation associated with activated macrophages may lead to the development of neoplasia, such as those found surrounding tuberculosis scars. (
  • Dysregulation of macrophage activation may cause increased inflammation and eventual neoplasia. (
  • New treatment strategies based on macrophage-related inflammation are also discussed. (
  • Macrophage s usually become more prevalent at the site of injury only after days or weeks and are a cellular hallmark of chronic inflammation. (
  • Macrophages are ubiquitous cells physiologically involved in a variety of processes including pathogen destruction, inflammation, tissue repair and remodeling. (
  • There is a growing understanding of the molecular drivers of inflammation and an appreciation that the resolution of inflammation is an active process rather than a passive return to homeostasis, and this has implications for our understanding of the role of macrophages in inflammation. (
  • An actively motile macrophage typically found in sites of inflammation. (
  • Unlike bone marrow macrophages, these cells live in the outer layer of the arterial wall, can self-replicate and help to heal the vessel after inflammation. (
  • Boosting the activity of the self-replicating macrophages that live in the outer layer of the arterial wall, helps reduce inflammation. (
  • The team thinks that once inflammation resolves, the self-renewing macrophages return to heal the damaged tissue. (
  • Our new model suggests we could possibly reduce inflammation by boosting the activity of these self-replicating macrophages. (
  • Beyond increasing inflammation and stimulating the immune system, macrophages also play an important anti-inflammatory role and can decrease immune reactions through the release of cytokines . (
  • Macrophages that encourage inflammation are called M1 macrophages, whereas those that decrease inflammation and encourage tissue repair are called M2 macrophages. (
  • [9] Also, testicular macrophages may participate in creating an immune privileged environment in the testis, and in mediating infertility during inflammation of the testis. (
  • In COPD, these macrophages are out of control and produce huge amounts of enzymes that break down lung tissue and more proteins that cause inflammation. (
  • Firstly, we could look at macrophages and predict which smokers will develop COPD and secondly, try and develop new treatments to stop the macrophages from producing all proteins that cause inflammation. (
  • The notion that inflammation in general and macrophage responses in particular affect physiological phenomena that were previously considered to be not immune-related has enhanced and broadened our understanding of macrophage function during inflammation and its resolution. (
  • This volume brings together 14 manuscripts that cover various aspects of macrophage function during inflammation and its resolution, as well as in several pathologic states for which a significant, long-lasting, macrophage-mediated immune response plays a significant role. (
  • Five provide an overview of macrophage function during inflammation and its resolution, with an emphasis on the modulatory role of particular elements in this response, such as apoptotic leukocytes, specific pathogens, hypoxia, and hormone receptors. (
  • The remaining seven manuscripts outline the role of macrophages during inflammation and its resolution in different tissues, including the lung, cardiovascular and adipose tissues, injured skeletal muscle and neuronal tissues, and synovial and oral cavities. (
  • Of the review articles that discuss the regulation of macrophage differentiation and function by discrete events, two cover the interaction between macrophages and apoptotic leukocytes during the resolution of inflammation. (
  • review the role of melanocortin receptor expression by macrophages in anti-inflammation and the resolution of inflammation, with attention given to melanocortin receptor agonists as therapeutic agents. (
  • Several review articles discuss the function of macrophages during inflammation and/or its resolution within distinct anatomical sites, taking into account the unique features of these tissue-specific macrophages, in particular the distinct environments in which they reside and their interactions with neighboring cells. (
  • Macrophages serve to maintain organ homeostasis in response to challenges from injury, inflammation, malignancy, particulate exposure, or infection. (
  • Macrophages not only regulate intestinal homeostasis by recognizing pathogens to control enteric infections but also employ negative feedback mechanisms to prevent chronic inflammation. (
  • In this review, we discuss some new findings on the properties of distinct populations of intestinal macrophages, how resolution of inflammation and tissue repair by macrophages could be promoted by type 2 cytokines as well as other therapeutic interventions, and highlight some challenges for translating these findings into the future for this exciting area of immunology research. (
  • Methods and Results- To explore the role of Notch signaling in inflammation, we examined the expression and activity of Notch pathway components in human primary macrophages in vitro and in atherosclerotic plaques. (
  • Notch3 knockdown during macrophage differentiation decreased the transcription of genes that promote inflammation, such as inducible nitric oxide synthase, pentraxin 3, Id1, and scavenger receptor-A. These in vitro findings correlate with results of quantitative immunohistochemistry, which demonstrated the presence of Dll4 and other Notch components within macrophages in atherosclerotic plaques. (
  • Conclusion- Dll4-triggered Notch signaling may mediate inflammatory responses in macrophages and promote inflammation. (
  • Clinical studies have established that lipid-lowering therapy reduces the onset of acute coronary events, 11,12 possibly in part through attenuation of inflammation and macrophage activition. (
  • Neutrophils and macrophages, as key mediators of inflammation, have defined functionally important roles in mammalian tissue repair. (
  • Moreover, we also sought to detail molecular regulators of inflammation in adult zebrafish and identified Wnt/β-catenin as a signaling pathway that regulates the injury microenvironment, inflammatory cell migration and macrophage phenotype. (
  • Macrophages are specialized immune cells that promote tissue inflammation, stimulate the immune system and rid the body of foreign debris, including cancer cells. (
  • Collectively, this new model combines findings derived from macrophage ontogeny, tissue macrophage biology and inflammation research in diseases. (
  • Cochain C and Zernecke A (2017) Macrophages in vascular inflammation and atherosclerosis. (
  • 2014) Embryonic and adult‐derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. (
  • tissues, where they develop into macrophages, the tissue phagocytes that constitute the reticuloendothelial system (or macrophage system). (
  • Macrophage s occur in almost all tissues of the body. (
  • Macrophages are essential components of mammalian tissues. (
  • This complements earlier findings by professors Geissmann and Mass that macrophages located in tissues develop very early during embryonic development, colonize the entire embryo and from then on maintain themselves through cell division. (
  • These new macrophage cells stay permanently in bodily tissues where they protect against invading germs and tumor cells by both engulfing and dissolving them, and by alerting other immune cells to the presence of invasive cells or organisms. (
  • Macrophages can enter various tissues under inflammatory or non-inflammatory conditions and assume different functions and phenotypes according to the cues they receive from the environment. (
  • Macrophages are present in all tissues and can fuse with other macrophages to differentiate into multinucleate osteoclasts (in bone) or giant cells (in multiple tissues), which play a central role in osteoporosis and chronic inflammatory diseases, respectively. (
  • Multinucleation is an essential step in the differentiation of osteoclasts, as mononucleated macrophages cannot resorb bone efficiently, and may also be essential in the differentiation of giant cells, which form in tissues in response to foreign particles. (
  • Recently, there has been considerable progress in our understanding of human macrophage biology in different tissues, including the intestines. (
  • Taken together, our results indicate that FBXW7 degrades EZH2 and increases Ccl2 and Ccl7 in CX3CR1hi macrophages, thereby promoting the recruitment of CX3CR1int proinflammatory MPhs into local colon tissues with colitis. (
  • The series of tests involved cultures of macrophages derived from human cells in vitro, which responded well to HDAC inhibitor treatment, as well as macrophages residing in mouse brain tissues. (
  • However the range of genes upregulated and functions carried out by macrophages in such hypoxic tissues are not fully understood. (
  • Macrophages are extremely versatile cells, distributed throughout all tissues, involved in numerous functions, and equipped with many sensing receptors and effector molecules. (
  • These diverse stress signals lead to further reprogramming of macrophages with different effect sizes and kinetics in macrophages derived from different tissues. (
  • Depending on the combination of MAFs signaling to the macrophage, the macrophage's activated phenotype becomes one of three major categories: classically activated, wound healing, or regulatory. (
  • Regulatory-phenotype macrophages have only recently been recognized as an important contributor to tissue microenvironments. (
  • Macrophages have been classified as M1 or M2 depending on the adaptive immune response that elicited the phenotype: Th1 or Th2 respectively. (
  • After receiving signaling from both IFNγ and TNF, macrophages acquire a phenotype with higher activity against both pathogens and tumor cells. (
  • Moreover, macrophages infiltrating the tumor microenvironment can transition towards a regulatory phenotype. (
  • In addition, the macrophage phenotype is greatly influenced by microenvironmental stimuli in the plaques and presents complex heterogeneity. (
  • Indeed, a limited tumor mass will probably be insufficient to educate macrophages into a suppressive phenotype. (
  • Current promising strategies to target tumor macrophages in vivo include pharmacological agents capable to re-polarize them towards a classically activated phenotype or to inhibit their suppressive properties. (
  • As a consequence of this, we put forward a suggestion for treatment based on rectifying the macrophage phenotype imbalance. (
  • Using a genetic mouse model of spherocytosis and single-cell RNA sequencing, we found that erythrophagocytosis skewed liver macrophages into an antiinflammatory phenotype that we defined as MarcohiHmoxhiMHC class IIlo erythrophagocytes. (
  • This phenotype transformation profoundly mitigated disease expression in a model of an anti-CD40-induced hyperinflammatory syndrome with necrotic hepatitis and in a nonalcoholic steatohepatitis model, representing 2 macrophage-driven sterile inflammatory diseases. (
  • Macrophage phenotype determines the cytokine secretion profile and tissue destruction capabilities of these cells. (
  • Whereas inflammatory synovial macrophages have not yet been classified into one phenotype or another it is widely known that TNFα and IL-l, characteristically released by M1 macrophages, are abundant in RA while IL-10 activity, characteristic of M2 macrophages, is somewhat diminished. (
  • Here we will briefly review our current understanding of macrophages and macrophage polarization in RA as well as the elements implicated in controlling polarization, such as cytokines and transcription factors like NFκB, IRFs and NR4A, and pro-resolving factors, such as LXA4 and other lipid mediators which may promote a non-inflammatory, pro-resolving phenotype, and may represent a novel therapeutic paradigm. (
  • And while the macrophage population shifts towards an alternatively activated phenotype, the inflammatory response subsides giving way to the "reparative/proliferative" phase. (
  • Hypoxia and ischaemia (poor blood flow) alter the phenotype of macrophages in a way that can promote development of disease, for example by causing the macrophage to secrete pro-inflammatory and pro-angiogenic (blood vessel growth stimulating) proteins. (
  • Interleukin 4, secreted by granulocytes after tissue damage or by adaptive immune cells within a Th2 response, causes macrophages to secrete minimal amounts of pro-inflammatory cytokines and to have lower activity against intracellular pathogens. (
  • Epithelial-mesenchymal transition has been found to be influenced by all types of macrophages, which cause both pro and anti-inflammatory responses that can promote EMT. (
  • Therefore, clarifying the macrophage-dependent inflammatory processes in atherosclerosis progression and exploring macrophage-targeted strategies to reduce the residual risk of atherosclerotic CVD have become a hot research topic in recent years. (
  • If you want inflammatory macrophages, simply inject 2 mls of thioglycollate broth into the peritoneum 3-4 days before harvest. (
  • Macrophages also participate in the immune response by producing and responding to inflammatory cytokines. (
  • This causes macrophages to swarm to the toxic cholesterol deposits, and become either M1 inflammatory or M2 healing cell types depending on the signals there. (
  • During inflammatory processes, for example after stroke, brain infections, multiple sclerosis or Alzheimer's disease, other macrophages come into play, which are recruited from the bone marrow. (
  • In the early "inflammatory" stage of MI, resident cardiac macrophages are replaced by classically activated macrophages derived from the bone marrow and spleen. (
  • In particular, there are more inflammatory cells called macrophages in the lungs of these patients. (
  • This binding leads to a pro-inflammatory cytokine response following engulfment by macrophages, implying a potential role for these elements in the etiology of systemic lupus erythematosus. (
  • Infiltrated macrophages and foam cells also participate in the inflammatory process by secretion of pro‐inflammatory cytokines, such as TNF‐α, IL‐1β and IL‐6. (
  • The data from this study demonstrate that macrophages are involved in OA, and that drugs targeting activated macrophages and their inflammatory pathways may be used to decrease OA symptoms and reduce joint deterioration. (
  • Etarfolatide is a folate receptor-targeted companion diagnostic imaging agent being developed as a non-invasive method to identify cells that over-express folate receptors, which allows imaging of activated macrophages that are associated with inflammatory diseases. (
  • Hence, macrophages are intriguing targets for immune-mediated therapies, especially when barrier function in the gut is compromised to trigger aberrant inflammatory responses, most notably during inflammatory bowel diseases. (
  • Background- Activated macrophages contribute to the pathogenesis of inflammatory diseases such as atherosclerosis. (
  • Thus, macrophages participate in an amplification cascade that sustains inflammatory responses in the atherosclerotic plaque and promote its structural instability and thrombogenicity. (
  • To begin to address these questions, we first tracked neutrophils ( lyzC + , mpo + ) and macrophages ( mpeg1 + ) in adult zebrafish following amputation of the tail fin, and detailed a migratory timecourse that revealed conserved elements of the inflammatory cell response with mammals. (
  • The healing effects of stem cells in spinal cord injury can be aided by their ability to hitch intercellular rides to specific anti-inflammatory cells called M2 macrophages, Yale researchers report. (
  • A potent anti-inflammatory response in bat macrophages may be lin. (
  • However, in bat macrophages, this antiviral, proinflammatory response was balanced by a sustained high-level transcription of the anti-inflammatory cytokine Il-10 , which was not observed in mouse, potentially resulting from adaptive regulation in bats. (
  • Wild-type macrophages calmed microglial inflammatory responses. (
  • What if the macrophages were tweaked to make them less inflammatory? (
  • Nox2 generates reactive oxygen species and in macrophages helps drive inflammatory response, whereas SOD1, oddly enough, mops up said ROS. (
  • In mice producing the SOD1 macrophages, microglia in the spinal cord began to express genes involved in a number of neuroprotective pathways, such as synaptogenesis signaling and oxidative phosphorylation, and they toned down inflammatory pathways, such as those involving TREM1signaling (see the image below). (
  • However, swapping peripheral macrophages for those overexpressing wild-type SOD1 (left column) turned down inflammatory pathways (arrowheads) and reversed a synaptogenic one (arrow). (
  • Lymphocytes, macrophages and neutrophils play an important role in the immune and inflammatory response. (
  • For a long time, macrophage activation was divided into either proinflammatory or anti‐inflammatory activation. (
  • We reproduced the antiinflammatory erythrophagocyte transformation in vitro by heme exposure of mouse and human macrophages, yielding a distinctive transcriptional signature that segregated heme-polarized from M1- and M2-polarized cells. (
  • Soluble Dll4 bound to human macrophages. (
  • Human macrophages are about 21 micrometres in diameter . (
  • This project will use the latest Molecular Biology techniques to investigate the responses of human macrophages to hypoxia, including such techniques as Real-Time RT PCR, Promoter / reporter gene analysis, and Western Blotting. (
  • We've discovered that a group of macrophages are created when the embryo is developing, before the bone marrow is functioning," said Clinton Robbins, a professor in the Faculty of Medicine's Departments of Laboratory Medicine and Pathobiology and Immunology. (
  • A team led by Professor Thomas Brocker , Director of the Institute of Immunology at LMU, has now shown that macrophages that function as a first line of defense in the innate immune system can also present antigens to T-cells, thus revealing a previously unknown role for macrophages in the induction of adaptive immune responses. (
  • Sivanjah's photo visualising macrophages in the adult mouse testis has been selected to be displayed at the inaugural Day of Immunology photography exhibition. (
  • The paradigm shift from a bipolar to a multidimensional model of macrophage activation required large data and computational modelling, illustrating the power of systems immunology to understand immune cell phenotypes and function. (
  • Macrophages, the major immune cell population in atherosclerotic lesions, have been shown to play critical roles in all stages of atherosclerosis, including the initiation and progression of advanced atherosclerosis. (
  • This article reviews the functions of macrophages in different stages of atherosclerosis, as well as the phenotypes and functions of macrophage subsets. (
  • Macrophages, the major immune cell population in the arterial plaques, have been suggested to play a central role in the immune responses and progression of atherosclerosis (Figure 1 ) [ 2 , 4 ]. (
  • Macrophage autophagy plays a protective role in advanced atherosclerosis," Cell Metabolism , 15:545-53, 2012. (
  • This study is the first to connect autophagy in macrophages to protection against disease progression, says Rick Austin of the Thrombosis and Atherosclerosis Research Institute in Hamilton, Ontario, Canada, who was not involved in the research. (
  • When researchers fed mice predisposed to atherosclerosis a high-fat diet and also blocked autophagy, macrophages died at a higher rate and were not efficiently cleared by phagocytes, suggesting that autophagy may be protective against plaque rupture. (
  • Macrophages, as part of the innate immune response, are among the most important cell types in every stage of atherosclerosis. (
  • We therefore revisited the mechanism underlying macrophage accumulation in atherosclerosis. (
  • The microenvironment orchestrates macrophage proliferation through the involvement of scavenger receptor A (SR-A). Our study reveals macrophage proliferation as a key event in atherosclerosis and identifies macrophage self-renewal as a therapeutic target for cardiovascular disease. (
  • We know that while bone marrow macrophages remove bacteria, they can also cause atherosclerosis by entering the arterial wall and multiplying," said Rickvinder Besla, graduate student and co-lead author. (
  • Proinflammatory macrophages contribute importantly to a wide variety of pathological states including cancer, neurologic disorders such as Alzheimer's disease, and cardiovascular diseases ranging from atherosclerosis, in-stent stenosis, and arterial and valvular calcification to heart failure. (
  • In the context of atherosclerosis, activated macrophages participate critically in every stage of lesion progression, from fatty streak formation to the onset of acute thrombotic complications. (
  • Further understanding of mechanisms that trigger macrophage activation could lead to more effective therapeutic strategies for atherosclerosis and its acute complications. (
  • Efferocytosis by macrophages is thought to curb the progression of atherosclerosis, but the mechanistic insight of this process is lacking. (
  • We hypothesized that interference with these pathways in macrophages can improve atherosclerosis outcome. (
  • A macrophage-activating factor (MAF) is a lymphokine or other receptor based signal that primes macrophages towards cytotoxicity to tumors, cytokine secretion, or clearance of pathogens. (
  • These are macrophages, a type of immune cell, which promote tumor progression and mask tumors from the immune system's scrutiny. (
  • But as little as 20 minutes later, the drug had been taken up by macrophages within the tumors. (
  • Macrophages directly aid glioma cells by secreting the growth factor SPP1, which the team showed increases cancer cell survival and blood vessel formation to protect the tumors. (
  • Tumor-associated macrophages are a major constituent of malignant tumors and are known to stimulate key steps in tumor progression. (
  • A more complete understanding of macrophage diversity in tumors could lead to the development of more selective therapies to restore the formidable, anticancer functions of these cells. (
  • One type of immune cells, macrophages, is present both in tumors and in nearby noncancerous tissue, but the relationship between these two cell populations is unclear. (
  • Moreover, when they removed macrophages from the tumors but not the other mammary tissue, tumors shrank and cytotoxic T cells-another kind of immune cell that kills tumor cells-infiltrated the tumors. (
  • The researchers found that macrophage cells infiltrating pancreatic, mammary and lung tumors produce high levels of the proteases cathepsin B and S (Cts B and S), which enhances tumor growth and invasion. (
  • We have observed a highly significant link between the appearance of ανβ3 expressing tumors and the appearance of tumor-associated macrophages,' said Cheresh, associate director of innovation and industry alliances at UC San Diego Moores Cancer Center. (
  • Epigenetic pathways have been identified to play a key role in monocyte-to-macrophage differentiation and activation. (
  • In addition to histone modifications, we highlight that also DNA methylation is an important regulator in human monocyte-to-macrophage differentiation. (
  • During embryonic development of macrophages from erythromyeloid precursors, these cells receive differentiation signals guaranteeing cell lineage determination which - at least to a certain extend - will remain throughout the entire life of a cell, and these ontogeny‐determined cellular programmes influence macrophage activation. (
  • Dave: To isolate resident peritoneal macrophages, kill the mouse, and immediately inject the peritoneum with about 5 mls of pre-warmed HBSS or other media. (
  • Peritoneal macrophages were isolated from uninfected SJL/J mice, which had been treated once with silica, and transferred into SJL/J mice 2 days before low-dose EMC-D infection. (
  • Fresh living Bacillus Calmette-Guerin (BeG), injected i.v. into (C57BI/ 6xDBA/2)FI mice, activated peritoneal macrophages rendering them highly cytotoxic for tumor cells in vitro. (
  • Time course analysis during the 14 days following Candida-priming revealed that LF administration slightly increased the number of peritoneal exudate cells, and significantly enhanced the production of superoxide anion (O2(-)) and nitric oxide (NO) by peritoneal macrophages at day 7. (
  • Here, we examined the effect of treatment with UTP and UDP in mouse peritoneal macrophages infected with T. gondii tachyzoites. (
  • Macrophages engulf and digest microbes, cellular debris and tumor cells as part of an immune response, and they secrete cytokines that affect other cells. (
  • Through mechanisms that have not yet been well elucidated, this impairment in cytotoxic function leads to an excessive expansion and activation of cytotoxic cells, with hypersecretion of proinflammatory cytokines such as interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and macrophage-colony-stimulating factor (M-CSF). (
  • Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages and natural killer cells, the production of antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. (
  • 10 Additionally, macrophages secrete various proinflammatory cytokines such as interleukin-1β (IL-1β) that induce atherothrombosis-associated molecules and the activation of endothelial cells and smooth muscle cells. (
  • In cancer, tumor-associated macrophages (TAMs) are recruited to the tumor stroma in response to cytokines secreted by tumor cells, and are believed to facilitate tumor cell invasion and metastasis. (
  • IFNγ signaling can initially originate from Natural Killer (NK) cells, but adaptive immune cells are required to sustain a population of classically activated macrophages. (
  • According to this grouping there are classically activated macrophages, wound-healing macrophages (alternatively activated macrophages) and regulatory macrophages (Mregs). (
  • Tumor-associated macrophages may be any of these types, and they have been found to be important players in the tumor microenvironment. (
  • We've identified a symbiotic circuit that is activated in PTEN-deficient glioblastoma which creates a mutually supportive relationship between the cancer cell and macrophages that come into the tumor microenvironment and provide growth factor support for the tumor," DePinho said. (
  • To capture the cellular interactions of the tumor microenvironment with high-resolution imaging, we directly visualized tumor cells and their interactions with macrophages in zebrafish. (
  • 1-5 Macrophages adapt to the local microenvironment and acquire various functions associated with physiological and pathological processes. (
  • Macrophages and Microglia in Brain Malignancies, Tumor Microenvironment and Myelomonocytic Cells Subhra K. Biswas, IntechOpen, DOI: 10.5772/35163. (
  • This model showcases the capability of macrophages of integrating signals they derive from their microenvironment to signal input‐specific functional programmes. (
  • Macrophages integrate signals from their microenvironment, which results in signal input‐specific functional outcomes. (
  • Then, macrophage proliferation becomes the predominant replenishment mechanism in advanced plaques [ 6 ]. (
  • [ 1 ] Macrophage activation syndrome is characterized by pancytopenia, liver insufficiency, coagulopathy, and neurologic symptoms and is thought to be caused by the activation and uncontrolled proliferation of T lymphocytes and well-differentiated macrophages, leading to widespread hemophagocytosis and cytokine overproduction. (
  • Replenishment of macrophages in these experimental atheromata depends predominantly on local macrophage proliferation rather than monocyte influx. (
  • 1,6-9 Moreover, macrophage proliferation may contribute to development of the inflamed plaque. (
  • At some sites such as the testis, macrophages have been shown to populate the organ through proliferation. (
  • We identified stage-dependent functional roles of macrophages in mediating fin tissue outgrowth and bony ray patterning, in part through modulating levels of blastema proliferation. (
  • These macrophages are defined by tissue and nerve type, are seeded in part prenatally, and self-maintain via proliferation. (
  • This amino acid has been shown to play a role in lymphocyte proliferation, cytokine production by lymphocytes and macrophages and phagocytosis and superoxide production by macrophages and neutrophils. (
  • These cells, called macrophages, are constituents of the reticuloendothelial system and are found in the lymph nodes, in the intestinal tract, and as free-wandering and fixed cells. (
  • Our immune systems can change as we get older, and now researchers at Washington University School of Medicine in St. Louis have found that as immune cells called macrophages age, the changes in those older cells can increase the risks for age-related macular degeneration, a major cause of blindness in the united states. (
  • A bacterial pathogen that typically multiplies outside of host cells can enter and induce the destruction of cells called macrophages, according to a study published June 20 in the open-access journal PLOS Pathogens by Anne-Béatrice Blanc-Potard of the Université de Montpellier in France, and colleagues. (
  • Researchers have known for years that HIV can infect specialized immune system cells called macrophages, but new research suggests these cells may play a larger role in HIV infection than previously believed. (
  • In conclusion, LF feeding augmented the activities of macrophages in a manner dependent on Candida-priming and these effects may be related to enhanced cytokine levels. (
  • Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine released from T-cells and macrophages. (
  • Macrophages are a type of phagocyte and belong to the congenital immune system, where they have a key role to play in defending against infection by intracellular pathogens such as those which cause tuberculosis, Legionnaires' disease or Q fever. (
  • This study not only adds iron homeostasis to the list of metabolic processes influenced by ERRγ but also suggests that preventing or reversing the iron accumulation that occurs in macrophages because of IL-6-induced hypoferremia might be a way to treat infection by S . typhimurium and other intracellular pathogens. (
  • Macrophages are normally the first immune cells in the body that come into contact with invading pathogens. (
  • Long recognized as an evolutionarily ancient cell type involved in tissue homeostasis and immune defense against pathogens, macrophages are being rediscovered as regulators of several diseases, including cancer. (
  • Macrophages are tissue-resident innate immune cells important in homeostasis and host defense against pathogens ( 1 ). (
  • Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) can control cancer growth and exist in almost all solid neoplasms. (
  • Tumor-associated macrophages (TAMs) can stimulate tumor growth ( 1 ⇓ ⇓ - 4 ), and their density is associated with adverse outcomes and shorter survival in several cancer types, including breast cancer, Hodgkin lymphoma, and lung adenocarcinoma ( 5 ⇓ ⇓ - 8 ). (
  • Here we show that in mice, mammary tumor growth induces the accumulation of tumor-associated macrophages (TAMs) that are phenotypically and functionally distinct from mammary tissue macrophages (MTMs). (
  • In their upcoming G&D paper, Dr. Joyce and colleagues delineate how tumor-associated macrophages (TAMs) promote tumor growth and invasion. (
  • Using the ανβ3 antibody LM609, Cheresh and his team exploited the appearance of ανβ3 receptors on tumor cells to redirect tumor-associated macrophages (TAMs) into recognizing and killing ανβ3 expressing tumor cells. (
  • However, it is also becoming evident that some myeloid-directed glioma therapies may only be beneficial for distinct subclasses of gliomas and that a more cell-type-specific manipulation of either microglia or macrophages may improve therapeutic outcomes. (
  • Lastly, we describe the therapeutic potential of cardiac macrophages in the context of cell-mediated cardio-protection. (
  • These data represent a preferential apoptotic signaling pathway of macrophages as specific target points for the prevention and therapeutic modulation of periprosthetic osteolysis. (
  • Tumor-associated macrophages may thus be an important therapeutic target. (
  • The therapeutic antibody we are utilizing is bridging the macrophage to the ανβ3-expressing tumor cell as a target. (
  • An additional, alternative strategy has also been proposed: to make use of the tendency of macrophages to accumulate in diseased sites to use them as delivery systems to carry therapeutic molecules, such as gene therapy DNA constructs, into these sites. (
  • The mechanism by which the spleen was able to maintain its reservoir capacity throughout tumor progression involved, in part, local accumulation in the splenic red pulp of typically rare extramedullary hematopoietic stem and progenitor cells, notably granulocyte and macrophage progenitors, which produced CD11b + Ly-6C hi monocytic and CD11b + Ly-6G hi granulocytic cells locally. (
  • The objective of this study was to identify the apoptotic mechanism of macrophages, and to explore the relationship between the apoptotic pathways and progression of osteolysis. (
  • Our results demonstrated that the majority of wear particles within osteolytic interface membrane was in the 30-60 nm range, and that macrophage apoptotic ratio increased along with osteolysis progression. (
  • In the February 1st issue of G&D , Dr. Johanna Joyce and colleagues at Memorial Sloan Kettering Cancer Center lend new insight into the mechanism by which tumor-associated macrophages promote malignant progression. (
  • The wild-type macrophages were unable to slow microglial activation or disease progression. (
  • A greater understanding of the role macrophages play in disease processes will enable the development of strategies to block their ability to carry out pro-disease functions, in order to slow disease progression. (
  • This Review discusses current knowledge of the developmental origins of various macrophage populations and the non-canonical functions of macrophages in development, regeneration and tissue repair. (
  • Macrophages and neutrophils participate in defense mechanisms that protect the host against injury and infection. (
  • Our understanding of the origins of tissue macrophages and neutrophils, going back to self-renewing hematopoietic stem cells (HSCs), is largely based on studies not involving cancer ( 10 ⇓ ⇓ - 13 ). (
  • Macrophages and neutrophils: dynamic duo or partners in crime? (
  • Unlike short-lived neutrophils , macrophages survive longer in the body, up to several months. (
  • The metabolic fate of glutamine in lymphocytes, macrophages and neutrophils will be discussed in the present paper. (
  • of lymph are lymphocytes and macrophages, the primary cells of the immune system with which the body defends itself from invasion by foreign microorganisms. (
  • For example, the HIV surface ligand gp120 binds to its receptor (CD4) on T lymphocytes and macrophages, and the hemagglutinin protein of influenza binds to its receptor (sialic acid) on epithelial cells. (
  • Eric Newsholme's laboratory was the first to show glutamine utilization by lymphocytes and macrophages. (
  • Indeed, it was not until the pioneering work of Eric Newsholme's laboratory in the 1980's that it was established that immune cells such as lymphocytes and macrophages could utilize glutamine at high rates in addition to glucose (3,4). (
  • A MAF can also alter the ability of macrophages to present MHC I antigen, participate in Th responses, and/or affect other immune responses. (
  • Activated by complex interaction with molecules on the surface of a macrophage or some other antigen-presenting cell, a helper T cell proliferates into two general subtypes, T H 1 and T H 2. (
  • This type of immunity is a long-term immunity which is acquired when a macrophage digests a microbe and presents the microbe's antigen on its surface to alert other white blood cells to the presence of the invading particle. (
  • To elucidate the role of macrophages in diabetic glomerulosclerosis (DGS), an immunohistologic study was performed using monoclonal antibodies to common leukocyte antigen (DAKO-LC), T cells (T3), B cells (CD22), and macrophages (MAC 387, Leu-M5, and EBM-11). (
  • The targeted antigen (yellow) is selectively taken up by macrophages (blue, red). (
  • Vaccine site biopsies manifested infiltrates of dendritic cells and macrophages among prostate tumor vaccine cells. (
  • The YCWP delivery system is effective at delivering DNA and transfecting macrophages and dendritic cells in vitro and in vivo, and is currently being used in preclinical studies to orally and systemically deliver genes for vaccines and transient gene therapy of a range of diseases. (
  • New work by LMU researchers demonstrates that macrophages can effectively substitute for so-called dendritic cells as primers of T-cell-dependent immune responses. (
  • In the study, Brocker and his team used several antigens that were specifically targeted to and processed by macrophages, but could not be taken up directly by dendritic cells. (
  • Further experiments showed that the targeted macrophages were actually able to prime a more comprehensive immune reaction than cross-presenting dendritic cells. (
  • The team of researchers observed changes in the mitochondrial metabolism of the macrophages caused by signalling pathways initiated by the lack of oxygen (hypoxia). (
  • Different strategies for inhibiting the pathological functions of myeloid cells in gliomas are explored, and blocking the tropism of microglia/macrophages to gliomas or manipulating the signal transduction pathways for immune cell activation has been successful in pre-clinical models. (
  • Apoptotic pathways of macrophages within osteolytic interface mem. (
  • Macrophage apoptosis in interface membrane, which occurs through either death receptor, mitochondrion, or endoplasmic reticulum (ER) stress pathways, has been suggested to play an important role in promoting osteolysis. (
  • However, how and why macrophage apoptosis originates and the correlation among these apoptotic pathways is not yet clear. (
  • Thus, our findings suggested that wear particles generated at implant interface can accelerate macrophage apoptosis through changes in apoptotic pathways and ultimately aggravate the symptom of osteolysis. (
  • Pathogenic antigens can bind to toll-like receptors that stimulate macrophage activation and response. (
  • Among the positive differentially expressed genes (DEGs), marker genes of the erythrophagocytic process are highlighted in red, genes associated with heme exposure and oxidative stress are highlighted in blue, and macrophage receptors are highlighted in green. (
  • We further show that macrophage accrual of aPD-1 mAbs depends both on the drug's Fc domain glycan and on Fcγ receptors (FcγRs) expressed by host myeloid cells and extend these findings to the human setting," the authors continued. (
  • Macrophages in culture express various Notch pathway components including all 4 receptors (Notch1 to Notch4). (
  • To explore this hypothesis we challenged macrophages from the greater mouse-eared bat, Myotis myotis and the house mouse, Mus musculus with toll like receptors (TLRs) ligands, lipopolysaccharides, LPS and polyinosinic-polycytidylic acid, Poly(I:C). Macrophages from both species presented a high level of mRNA induction of inferon β ( INF-β ), tumor necrosis factor ( TNF ) and interleukin-1 β ( Il-1β ). (
  • Our results suggest that the activity of P2Y host cell receptors controls T. gondii infection in macrophages, highlighting the importance of pyrimidinergic signaling for innate immune system response against infection. (
  • 11 January 2017 - UK-based newly formed immune-oncology company Macrophage Pharma Ltd has acquired global rights to a novel technology platform, Esterase Sensitive Motif, from Chroma Therapeutics Ltd. (
  • CAMBRIDGE, Mass. , May 16, 2017 /PRNewswire-USNewswire/ -- Claritas Genomics announces the launch of the Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS) Region of Interest test to its menu of exome based molecular diagnostic testing. (
  • Gordon S and Martinez‐Pomares L (2017) Physiological roles of macrophages. (
  • cell, known as an alveolar macrophage, resides on the internal surfaces of the air cavities of the alveoli, the alveolar ducts, and the bronchioles. (
  • Macrophages are part of mononuclear phagocytic system, and the alveolar macrophage is the first cell to encounter M. (
  • The effects of alpha emitting transuranic nuclides on the alveolar macrophage, and the use of this cell as a marker for investigating early radiation effects on the lung, have been studied. (
  • An accumulation of activated macrophages of this sort is termed a granuloma. (
  • A majority of macrophages are stationed at strategic points where microbial invasion or accumulation of foreign particles is likely to occur. (
  • Foam cells are lipid‐loaded macrophages that are generated from the massive uptake of modified low‐density lipoproteins and the intracytoplasmatic accumulation of cholesteryl esters. (
  • b) Microphotograph of the earliest stage of an atherosclerotic lesion, the fatty streak, after staining with oil‐red O. The fatty streak is characterised by subendothelial accumulation of macrophages/foam cells, which contain massive amounts of lipids, as indicated by oil‐red O staining. (
  • Fbxw7 deficiency resulted in decreased production of the chemokines CCL2 and CCL7 by colonic CX3CR1hi resident macrophages and reduced the accumulation of CX3CR1int proinflammatory MPhs in colitis-affected colon tissue. (
  • The information obtained from these initial experiments will then be used to design, implement and test novel gene therapy strategies with a view to designing a Gene Therapy procedure to improve the outcome of diseases associated with hypoxia and macrophage accumulation. (
  • In addition, the phenotypes of the macrophages in a certain environment play a fundamental role in determining the immune activity and response within the tissue. (
  • We describe a mathematical model which offers a possible explanation for diabetic wound healing in terms of the distribution of macrophage phenotypes being altered in the diabetic patient compared to normal wound repair. (
  • The second manuscript by Ariel and Serhan (2012) reviews the impact of apoptotic cell sensing and disposal by macrophages on the switches in functional phenotypes displayed by these cells. (
  • Monocyte and macrophage phenotypes: a look beyond systemic sclerosis. (
  • Macrophages are part of the innate immune system and essential for brain development and function. (
  • In the innate immune system, macrophages are the second-line of defense, after the physical (skin, mucous coating of the gut) and chemical barriers (anti-microbial molecules like lysozymes) provide the first line of defense. (
  • and transgenic models of macrophage depletion and macrophage targeting. (
  • The depletion of macrophages by treatment with the combined anti-Mac-1 and anti-Mac-2 monoclonal antibodies after a single administration of CFA, Car, or silica resulted in almost complete prevention of β-cell destruction in EMC-D virus-infected mice. (
  • Cell depletion studies show that macrophages regulate multiple key aspects of a mammalian epimorphic regenerative response, including wound closure, bone histolysis, blastema formation and redifferentiation. (
  • Making macrophages in atherosclerotic plaques digest spent organelles instead of dying may help keep plaques stable. (
  • MACROPHAGE AUTOPHAGY: The autophagosomes within macrophages helps keep atherosclerotic plaques from bursting and causing blood clots. (
  • Atherosclerotic plaques can prompt heart attacks and strokes when lipid-containing macrophages inside them die and necrose, causing the plaque to rupture and clog blood vessels. (
  • Macrophages are white blood cells (leukocytes) which accumulate in hypoxic diseased sites such as cancer, atherosclerotic plaques, arthritic joints, infarcted heart tissue after heart attacks, and also in Tuberculosis granulomas. (
  • In studies on mice, this technology enabled the researchers to observe that shortly after a stroke, numerous macrophages that had migrated from the blood begin to attack dead and adjacent healthy brain tissue. (
  • With the help of their model study on mice, the researchers have now discovered that shortly after a stroke, numerous macrophages that had migrated from the blood begin to attack dead and adjacent healthy brain tissue. (
  • one employing a subset of yolk sac-derived, cardiac macrophages that have complete restorative capacity in the injured myocardium of neonatal mice, and in another example, post-conditioning of cardiac macrophages with cardiosphere-derived cells significantly improved patient's post-MI diagnoses. (
  • Furthermore, none of the mice in which macrophages were depleted by long-term treatment with silica and 10% of the mice treated with Car before virus infection became diabetic. (
  • On the basis of these observations, we conclude that macrophages are directly involved in the destruction of β-cells, leading to the development of clinical diabetes in EMC-D virus-infected mice. (
  • This study aimed to evaluate the effect of bovine LF feeding on peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans. (
  • LF administration facilitated NO production and Candida hyphal-growth inhibition by macrophages derived from Candida-primed mice but not non-primed mice, suggesting that the action of LF is dependent on the immune status of the host. (
  • Lactoferrin feeding augments peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans. (
  • Macrophages isolated from macrophage-specific ERK5 null mice exhibited reduced efferocytosis and levels of gene and protein expression of efferocytosis-related molecules. (
  • In this thesis we validated the role of the repressive H3K27me3 methyltransferase enhancer of the zeste homolog 2 (Ezh2) and lysine demethylase 6b (Kdm6b) in macrophage foam cells and atherosclerotic lesion development in mice. (
  • To see how wild-type macrophages would respond, Chiot ablated myeloid cells in approximately 50-day-old SOD1 G93A mice using the chemotherapy drug busulfan. (
  • While this was transient, becoming less pronounced as the disease progressed, symptoms started two weeks later than in mice with macrophages carrying mutant SOD1, and the mice flushed with the new macrophages lived about two weeks longer as well. (
  • Mice repopulated with Nox2-negative macrophages had similarly reduced microglial activation, developed motor symptoms later, and lived slightly longer than SOD1 G93A controls. (
  • The term bone marrow macrophages can refer to either naturally produced cells, or cells created in an in vitro environment, meaning that they're produced in a laboratory setting rather than made naturally in the body of a living animal. (
  • The term bone marrow-derived macrophages refers specifically to macrophage cells that are created in vitro. (
  • We further found that macrophages transfer cytoplasm to tumor cells upon cell contact in vitro. (
  • Methods and Results -When macrophages were fed apoptotic cells (ACs) or treated with pitavastatin in vitro , efferocytosis-related signaling and phagocytic capacity were upregulated in an ERK5 activity-dependent manner. (
  • Macrophages are important cells of the immune system that are formed in response to an infection or accumulating damaged or dead cells. (
  • In this way, macrophages provide a first line of defence in protecting the host from infection. (
  • The researchers from the University of Toronto have found that a specific type of tissue macrophage, a group of white blood cells that defend against infection, are created and operate separately from other macrophages that come from the bone marrow. (
  • Robbins and his team found that during infection these self-replicating macrophages leave the arterial wall, while macrophages from the bone marrow come in and engulf the bacteria. (
  • HIV-1 establishes latent infection in resting CD4 + T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. (
  • We knew that SAMHD1 is switched off when cells multiply, but macrophages do not multiply so it seemed unlikely that SAMHD1 would be switched off in these cells," said Professor Ravindra Gupta (UCL Infection & Immunity), the senior author of the paper. (
  • The researchers say that macrophages can be an important reservoir of HIV infection that lingers away from the reach of existing treatments. (
  • Once a macrophage is infected, it will continually produce the HIV virus, so cutting off that point of infection within the body could be an important step towards safeguarding the entire immune system. (
  • Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages. (
  • Our research suggests that macrophages are an underappreciated reservoir of virus in HIV infection," says study author Malcolm A. Martin, M.D., chief of NIAID's Laboratory of Molecular Microbiology. (
  • Most currently available treatments target HIV during its infection of T cells, but if the virus also infects and accumulates in large amounts in macrophages, additional drugs may be required. (
  • The researchers tested this idea by checking whether a potent reverse transcriptase (RT) inhibitor could control both the early T-cell and late macrophage stages of the SHIV infection. (
  • Using a novel method, scientists from Jena University Hospital, the University of Bonn and the Memorial Sloan Kettering Cancer Center in New York (USA) succeeded in visualizing macrophages that were formed in the bone marrow. (
  • The researchers were able to show that during a healthy mouse life, virtually no macrophages generated by bone marrow stem cells settle in the brain. (
  • [ 9 ] In a study of autopsy specimens of a child with SJIA-associated macrophage activation syndrome, the bone marrow was identified as the origin of increased serum IL-18. (
  • What Are Bone Marrow Macrophages? (
  • Bone marrow macrophages are a type of white blood cell , or leukocyte, that attack and digest invading bacteria, tumor cells, protozoa, which are single-celled organisms, and other hostile germs that can invade and infect a living host organism. (
  • As their name suggests, bone marrow macrophages are created in the marrow, or the inner tissue, of the bones of animals and humans. (
  • Macrophages can be created in a laboratory by artificially growing mammalian bone marrow. (
  • Hematopoiesis, which can also be spelled haematopoiesis, is the process by which the body naturally creates all the different types of blood cells, or blood components, including bone marrow macrophages. (
  • Bone marrow macrophages belong to the myelocyte lineage. (
  • Other positive macrophages can be found in the splenic red pulp, in the mesentric lymphoid paracortex, interfollicular areas of Peyer's patches and bone marrow. (
  • The intricate balance between phenotypically heterogeneous populations of macrophages in the heart have profound and highly orchestrated effects during different phases of myocardial infarction. (
  • Our job now is to get a better understanding of what these different macrophage populations are doing. (
  • Macrophages are one of the most versatile cell populations within multicellular organisms. (
  • Our findings point to a pathway that regulates macrophage functions to link erythrocyte homeostasis with innate immunity. (
  • Until now, receptor ligation has been understood as being the central mechanism that regulates macrophage function. (
  • The same process of rapid antibody binding to PD-1 molecules on CD8 T cells, followed by macrophage uptake, was observed in models of melanoma and lung cancer. (
  • To determine how the antibodies were being removed from T cells, the researchers first confirmed that the macrophages neither expressed PD-1 molecules nor did they take up antibody not bound to T cells. (
  • Thus, we present a model in which macrophage/tumor cell contact allows for the transfer of cytoplasmic molecules from macrophages to tumor cells corresponding to increased tumor cell motility and dissemination. (
  • show that macrophages transfer cytoplasmic molecules to tumor cells via cell contact in zebrafish and mouse. (
  • Matrix-degrading enzymes and prothrombotic molecules elaborated from activated macrophages may promote plaque disruption and subsequent thrombosis. (
  • Molecules that upregulate ERK5 and its signaling in macrophages may be good drug targets for suppressing cardiovascular diseases. (
  • Cutting-edge and comprehensive, Macrophages: Methods and Protocols is a valuable resource for researchers who are interested in studying macrophages on an experimental level. (
  • The researchers discovered that fewer metabolites are produced in the citric acid cycle under hypoxic conditions, leading to a reduced rate of reproduction among bacteria in macrophages. (
  • The researchers found that a stroke initially attracted fewer macrophages into the brain when the Cxcr4 function was missing. (
  • A common genetic deficiency empowers glioblastoma to broadcast a molecular message to the wrong type of immune cell, summoning macrophages that protect and nurture the brain tumor instead of attacking it, researchers at The University of Texas MD Anderson Cancer Center report in Cancer Cell . (
  • Next, the researchers will study how these resident macrophages interact with their tissue environment and exactly what role they might play in cardiovascular disease. (
  • Comprehensive and practical, Macrophage Migration Inhibitory Factor: Methods and Protocols is a valuable resource that will help researchers gain a new understanding of MIF biology in health and disease. (
  • A team led by UCL researchers has identified how HIV is able to infect macrophages, a type of white blood cell integral to the immune system, despite the presence of a protective protein. (
  • When the researchers examined lymphoid organs such as lymph nodes and spleen for the source of the remaining virus, they found that 95 percent of the virus-producing cells were macrophages and only 1 to 2 percent were T cells. (
  • This volume looks at--and discusses the techniques of--a range of areas in biology in which macrophage migration inhibitory factor (MIF) is studied. (
  • In addition, tissue-resident macrophages have many tissue-specific functional characteristics, which are a reflection of distinct gene-expression programs. (
  • Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. (
  • Thus, they are markedly distinct from monocyte-derived macrophages invading after local disturbance of nerve integrity. (
  • Tissue biology perspective on macrophages. (
  • Here we discuss the emerging views of macrophage biology from evolutionary, developmental and homeostatic perspectives. (
  • In this review we discuss the discovery of TNFα and its actions especially in regulating macrophage biology. (
  • Nudging macrophages to respond to stress by breaking down their own organelles-a process called autophagy-can keep plaques stable by reducing macrophage death and by making it easier for phagocytes to recognize and remove those that do die. (
  • These findings, as well as those reported previously, suggest that the melanoma cell provides the RNA, protein, and precursors which initiate macrophage DNA synthesis. (
  • Toll-like receptor agonists may also cause macrophage activation. (
  • Macrophage activation syndrome (MAS) is a life-threatening complication of rheumatic disease that, for unknown reasons, occurs much more frequently in individuals with systemic juvenile idiopathic arthritis (SJIA) and in those with adult-onset Still disease. (
  • Macrophage activation syndrome is characterized by a highly stimulated but ineffective immune response. (
  • Recent studies have shown that MUNC 13-4 polymorphisms are associated with macrophage activation syndrome in some patients with SJIA. (
  • These findings were supported by a recent study of hepatic biopsy samples in patients with various types of HLH, including macrophage activation syndrome. (
  • The hyperproduction of IL-18, which strongly induces T helper cell 1 (Th-1) responses and IFN-γ production and enhances NK cells cytotoxicity, and an imbalance between levels of biologically active free IL-18 and levels of the IL-18-binding protein may also play a role in secondary hemophagocytic syndromes, including macrophage activation syndrome. (
  • Moreover, very high levels of IL-18 have been reported in 2 patients with SJIA and macrophage activation syndrome. (
  • Macrophages can be classified on basis of the fundamental function and activation. (
  • Macrophage elasticity is dependent upon actin polymerization and small rhoGTPase activation, but functional effects of elasticity are not predicted by examination of gene expression profiles alone. (
  • Macrophage responses to PPAR and LXR activation. (
  • Although Notch signaling participates in various aspects of immunity, its role in macrophage activation remains undetermined. (
  • Therefore, it is of utmost importance to understand how macrophage activation is regulated and orchestrated. (
  • However, with the advent of the generation of high‐throughput data, this view on macrophage activation has dramatically changed by realising the enormous plasticity of these cells. (
  • To describe such plasticity, and based on computational modelling of transcriptome data, we have introduced the multidimensional model of macrophage activation. (
  • The multidimensional model of macrophage activation describes the input‐specific cellular programming of macrophages in response to stimulation. (
  • Multidimensional model of macrophage activation. (
  • The overall fate and cellular programming of a macrophage under homeostatic conditions are mainly determined by tissue‐specific microenvironmental signals determining the general activation state and functionality of a macrophage. (
  • Ginhoux F, Schultze JL, Murray PJ, Ochando J and Biswas SK (2015) New insights into the multidimensional concept of macrophage ontogeny, activation and function. (
  • Detail of the MGH investigation appeared May 10 in the journal Science Translational Medicine, in an article entitled "In Vivo Imaging Reveals a Tumor-Associated Macrophage-Mediated Resistance Pathway in Anti-PD-1 Therapy. (
  • They not only defined the pathway that brings macrophages into glioblastoma, but also pinpointed a growth factor secreted by the macrophages that in turn protects cancer cells from programmed cell death and fuels the growth of new blood vessels. (
  • Taken together, these data demonstrate an unanticipated role for cell elasticity as a common pathway by which mechanical and biologic factors determine macrophage function. (
  • In murine atherosclerotic lesions, we found that macrophages turn over rapidly, after 4 weeks. (
  • Using a Cre/LoxP strategy, we found that macrophages transfer cytoplasm to tumor cells in zebrafish and mouse models. (
  • A new international study has made an important discovery about the key role of macrophages, a type of immune cell, in systemic sclerosis (SSc), a chronic autoimmune disease which currently has no cure. (
  • While pickpocketing is becoming a lost art in our cities, it is still practiced at the cellular level by macrophages. (
  • Cellular immune responses were assessed indelayed type hypersensitivity (DTH) assay, macrophage engulfment assay, cyclophosphamide induced neutropenic test and nitric oxide (NO) production assay. (
  • Basic scientists in France have recently discovered that macrophages located in urethral tissue can contribute to cellular HIV reservoirs, and that the quantity of these specific immune cells is surprisingly high. (
  • In the second line of defense, after foreign substances gain access to the body, phagocytic cells (macrophages and neutrophil granulocytes) can engulf (phagocytose) foreign substances. (
  • Macrophages are important in the body's defense against disease and are found mainly in the spleen, lymph nodes, and liver. (
  • In contrast, the responses to the B-cell mitogen LPS of unfractionated and macrophage-depleted spleen cells were not affected or significantly enhanced depending on the dose of BCG injected. (
  • The role of macrophages during tumor development is ambiguous. (
  • To study the role of mast cell and macrophage counts in the planning of treatment and predicting the treatment outcome. (
  • Thus, clarification of the role of DC-STAMP in macrophage fusion will be a major step toward a better understanding of fusion and will bring together several areas of research. (
  • Airway macrophages (AMs) are important cell types in the lung, playing a pivotal role in host defense. (
  • These experiments suggested that melanoma proteins played an important role in the initiation of macrophage DNA synthesis. (