Macrophages: 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.)Macrophage Activation: 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.Macrophages, Peritoneal: Mononuclear phagocytes derived from bone marrow precursors but resident in the peritoneum.Macrophages, Alveolar: 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.Phagocytosis: The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).Macrophage Colony-Stimulating Factor: 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, Cultured: 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.Lipopolysaccharides: 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)Mice, Inbred C57BLMonocytes: 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.Macrophage Migration-Inhibitory Factors: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Tumor Necrosis Factor-alpha: 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.Mice, Inbred BALB CCytokines: 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.Mice, Knockout: 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.Peritoneal Cavity: 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.Thioglycolates: Organic esters of thioglycolic acid (HS-CH2COOH).Macrophage Inflammatory Proteins: 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.Inflammation: 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.Antigens, Differentiation, Myelomonocytic: 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.Ascitic Fluid: The serous fluid of ASCITES, the accumulation of fluids in the PERITONEAL CAVITY.Receptor, Macrophage Colony-Stimulating Factor: 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, Messenger: 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.Interferon-gamma: 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.Clodronic Acid: A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification.Mice, Inbred C3HScavenger Receptors, Class A: A family of scavenger receptors that mediate the influx of LIPIDS into MACROPHAGES and are involved in FOAM CELL formation.Phagosomes: 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.Gene Expression Regulation: 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.Nitric Oxide: 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.Pulmonary Alveoli: 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.Nitric Oxide Synthase Type II: 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.Signal Transduction: 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.Spleen: An encapsulated lymphatic organ through which venous blood filters.Macrophage-Activating Factors: 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.ZymosanBone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Lipoproteins, LDL: 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.Mannose-Binding Lectins: A subclass of lectins that are specific for CARBOHYDRATES that contain MANNOSE.Chemokine CCL2: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Receptors, Scavenger: 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.Flow Cytometry: 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.NF-kappa B: 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.Toll-Like Receptor 4: A pattern recognition receptor that interacts with LYMPHOCYTE ANTIGEN 96 and LIPOPOLYSACCHARIDES. It mediates cellular responses to GRAM-NEGATIVE BACTERIA.Receptors, Cell Surface: 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.Atherosclerosis: A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.Disease Models, Animal: 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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Immunity, Innate: 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.Neutrophils: 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.Interleukin-6: 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.Receptors, Immunologic: 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.Interleukin-1: 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.Inflammation Mediators: The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).Apoptosis: 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.Granulocyte-Macrophage Colony-Stimulating Factor: 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.T-Lymphocytes: 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.Antigens, CD: 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.Interleukin-10: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Mice, Inbred Strains: 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.Reverse Transcriptase Polymerase Chain Reaction: 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.Bronchoalveolar Lavage Fluid: 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.Chemokines: 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.Lysosomes: 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)Up-Regulation: 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.Phagocytes: Cells that can carry out the process of PHAGOCYTOSIS.Chemokine CCL4: 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.Chemokine CCL3: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Arginase: A ureahydrolase that catalyzes the hydrolysis of arginine or canavanine to yield L-ornithine (ORNITHINE) and urea. Deficiency of this enzyme causes HYPERARGININEMIA. EC 3.5.3.1.Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Receptors, Fc: 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.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Lectins, C-Type: 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.Toll-Like Receptor 2: 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.Interleukin-1beta: 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.Cell Count: The number of CELLS of a specific kind, usually measured per unit volume or area of sample.Mycobacterium bovis: The bovine variety of the tubercle bacillus. It is called also Mycobacterium tuberculosis var. bovis.Monokines: Soluble mediators of the immune response that are neither antibodies nor complement. They are produced largely, but not exclusively, by monocytes and macrophages.Opsonin Proteins: 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.Pinocytosis: The engulfing of liquids by cells by a process of invagination and closure of the cell membrane to form fluid-filled vacuoles.Mycobacterium tuberculosis: 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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Arteriosclerosis: 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.Apolipoproteins E: 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.Receptors, IgG: 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).Molecular Sequence Data: 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.Dinoprostone: 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.Cell Survival: 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.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Dendritic Cells: 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).Coculture Techniques: 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.Lymphocytes: 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.Toll-Like Receptors: 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.Blotting, Western: 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.ATP Binding Cassette Transporter 1: 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.Chemokine CXCL2: A CXC chemokine that is synthesized by activated MONOCYTES and NEUTROPHILS. It has specificity for CXCR2 RECEPTORS.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Microscopy, Electron: 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.Superoxides: 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.Macrophage-1 Antigen: 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.Interleukin-12: 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.Listeria monocytogenes: 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.Kupffer Cells: 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, Monoclonal: Antibodies produced by a single clone of cells.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Legionella pneumophila: 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.Matrix Metalloproteinase 12: A secreted matrix metalloproteinase which is highly expressed by MACROPHAGES where it may play a role in INFLAMMATION and WOUND HEALING.Mycobacterium avium: 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, Conditioned: 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).Antigens, CD11b: 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.Cell Adhesion: Adherence of cells to surfaces or to other cells.Down-Regulation: 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.U937 Cells: 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.Rabbits: 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.Enzyme-Linked Immunosorbent Assay: 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.Antigens, CD36: 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.Membrane Proteins: 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.Virus Replication: 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.Virulence: 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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Kinetics: The rate dynamics in chemical or physical systems.Cytotoxicity, Immunologic: 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.Microglia: 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.Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents.Histocompatibility Antigens Class II: 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.Cell Migration Assays, Macrophage: 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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Immunity, Cellular: 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.Sialic Acid Binding Ig-like Lectin 1: 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.Myeloid Differentiation Factor 88: 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.Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient.Cholesterol Esters: 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.Nitrites: 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)HIV-1: 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, Differentiation: 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.Anti-Inflammatory Agents: Substances that reduce or suppress INFLAMMATION.Interleukin-4: 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.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Scavenger Receptors, Class B: A family of scavenger receptors that are predominately localized to CAVEOLAE of the PLASMA MEMBRANE and bind HIGH DENSITY LIPOPROTEINS.Lymphocyte Activation: 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.Cell Migration Inhibition: 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.Cell SeparationMice, Inbred CBALeukocytes: White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).Leishmania: 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.Mice, Inbred ICRChemotactic Factors: 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.Enzyme Activation: 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.Propionibacterium acnes: 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.Silicon Dioxide: 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, LDL: 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.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Chemotaxis, Leukocyte: The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.Cell Communication: 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.Caspase 1: 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.Endotoxins: 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.Cyclooxygenase 2: 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.Receptors, Complement: Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2.Receptors, Lipoprotein: 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.Receptors, CCR2: 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.Listeriosis: Infections with bacteria of the genus LISTERIA.Colony-Stimulating Factors: 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, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Latex: 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.Reactive Oxygen Species: 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.Respiratory Burst: 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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Leishmania mexicana: 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.Liposomes: 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.Intramolecular Oxidoreductases: 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.p38 Mitogen-Activated Protein Kinases: 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.Leishmania donovani: 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.ATP-Binding Cassette Transporters: 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.Interleukin-8: 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.Enzyme Induction: 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.Fluorescent Antibody Technique: 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.Leukocytes, Mononuclear: 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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Hydrogen Peroxide: 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.Chemokine CCL5: 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.Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity.Adjuvants, Immunologic: 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.Amino Acid Sequence: 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.Guinea Pigs: 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.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Specific Pathogen-Free Organisms: Animals or humans raised in the absence of a particular disease-causing virus or other microorganism. Less frequently plants are cultivated pathogen-free.Interleukin-12 Subunit p40: 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.Transfection: 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.Mice, Inbred DBAImmunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Orphan Nuclear Receptors: 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.Antibodies: 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).

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)

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 ...
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 ...
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 ...
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 ...
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) 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 ...
Obesity is associated with low-grade chronic inflammation without bacterial or viral infection, but the triggers and molecular mechanisms that lead to obesity-associated metabolic inflammation remain to be further explored. Although recent studies demonstrated palmitate triggered thioglycollate-elicited macrophage death under the stimulation of Gram-negative bacteria-derived LPS (39, 40), it did not explain the sterile inflammation associated with obesity, and it also raised concerns regarding physiology and activated status of these thioglycollate-activated macrophages (41). In this article, we report that when various dietary FAs were uptaken by stable macrophage cell lines or primary BMMs, only sFAs (e.g., PA, SA) were metabolized to produce Cers to induce macrophage cell death. Most importantly, we identified A-FABP as a new molecular sensor in mediating excess sFA-induced Cer production and in promoting macrophage cell death, thus contributing to the sterile chronic inflammation in ...
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
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) ...
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 ...
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,
Glass, C.K. (2001) Potential roles of the peroxisome proliferator-activated receptorγ in macrophage biology and atherosclerosis. Journal of Endo-crinology, 169, 461-464. doi10.1677/joe.0.1690461
Macrophages in the gastrointestinal mucosa represent the largest pool of tissue macrophages in the body. In order to maintain mucosal homeostasis, resident intestinal macrophages uniquely do not express the lipopolysaccharide (LPS) co-receptor CD14 or the IgA (CD89) and IgG (CD16, 32, and 64) receptors, yet prominently display Toll-like receptors (TLRs) 3-9. Remarkably, intestinal macrophages also do not produce proinflammatory cytokines in response to TLR ligands, likely because of extracellular matrix (stromal) transforming growth factor-β (TGF-β) dysregulation of nuclear factor (NF)-κB signal proteins and, via Smad signaling, expression of IBα, thereby inhibiting NF-κB-mediated activities. Thus, in noninflamed mucosa, resident macrophages are inflammation anergic but retain avid scavenger and host defense function, an ideal profile for macrophages in close proximity to gut microbiota. In the event of impaired epithelial integrity during intestinal infection or inflammation, however, ...
Macrophages are remarkably plastic cells which in order to adapt to different tissue microenvironments can assume a range of different phenotypes. Accordingly, macrophages can exhibit either pro- or anti-inflammatory phenotypes and are routinely classified into M1 (classically activated) phenotype and M2 (alternatively activated) phenotype.[4] According to this classification, macrophages acquire M1 phenotype following in vitro stimulation with interferon gamma (IFN-γ) alone or in combination with TLR ligands (e.g. lipopolysaccharide (LPS)) whereas macrophages acquire M2 phenotype after in vitro exposure to IL-4 and IL-13. M1 macrophages secrete high levels of proinflammatory cytokines (e.g. tumor necrosis factor (TNF-α), IL-6, IL-1β) and generate reactive oxygen and nitrogen species such as nitric oxide via activation of inducible nitric oxide synthase (iNOS). Conversely, M2 macrophages activate arginase 1 (Arg1) that blocks iNOS activity and therefore inhibits nitric oxide production. They ...
The hypothesis that distinct populations of macrophages are associated with muscle necrosis and regeneration was examined in Wistar rat soleus muscle after 10 days of hindlimb suspension and 2, 4, and 7 days after the resumption of weight bearing. Necrosis was identified using histological features, such as muscle fiber infiltration, and regeneration was identified using immunohistochemical techniques for developmental myosin heavy chain (dMHC). Light-microscopic observations show that necrotic fibers in 2-day reloaded soleus muscle were invaded by ED1+ and Ia+ macrophages. The number of invaded fibers in muscles reloaded for 2 days increased to 2.8/mm2 compared with 0.2/mm2 in age-matched normal muscle but returned to control values by the 4th day of resumed weight bearing. In the interstitial spaces of 2-day recovery muscle, ED1+ and Ia+ macrophages numbered 369 and 332/mm2, respectively, compared with 12 and 72/mm2, respectively, in control soleus. After 7 days of reloading, the number of ED1+ cells
Tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) are significant components of the microenvironment of solid tumors in the majority of cancers. TAMs sequentially develop from monocytes into functional macrophages. In each differentiation stage, TAMs obtain various immunosuppressive functions to maintain the tumor microenvironment (e.g., expression of immune checkpoint molecules, production of Treg-related chemokines and cytokines, production of arginase I). Although the main population of TAMs is immunosuppressive M2 macrophages, TAMs can be modulated into M1-type macrophages in each differential stage, leading to the suppression of tumor growth. Because the administration of certain drugs or stromal factors can stimulate TAMs to produce specific chemokines, leading to the recruitment of various tumor-infiltrating lymphocytes, TAMs can serve as targets for cancer immunotherapy. In this review, we discuss the differentiation, activation, and immunosuppressive function of TAMs, as well
Cell Culture. The murine macrophage cell line J774A.1 was grown in RPMI 1640 medium (Invitrogen, Carlsbad, CA) supplemented with 100 U/ml penicillin, 100 μg/ml streptomycin, 50 μg/ml gentamicin, 20 U/ml polymyxin B, and 10% fetal bovine serum. Alternatively, peritoneal macrophages were isolated 5 days after injection of 2 ml of Brewers thioglycolate medium (Sigma-Aldrich, St. Louis, MO) into the peritoneal cavity of C56BL/6 mice as reported previously (McCarron et al., 1984). Primary macrophages were added to culture flasks and allowed to adhere for 2 h at 37°C. Nonadherent cells were removed by three washes of warm medium. Adherent cells were ,99% macrophages as assessed by immunocytochemical detection of the macrophage marker F4/80 (anti-F4/80, clone Cl:A3-1; Serotec, Oxford, UK). Smooth muscle cells were isolated from mouse or rabbit aorta by collagenase type 2 (Worthington, Lakewood, NJ) and elastase (Sigma-Aldrich) digestion (60-90 min at 37°C) at 300 and 5 U/ml final concentration, ...
Diabetic cardiomyopathy (DCM) is a common complication of diabetes and is characterized by chronic myocardial inflammation. Mesenchymal stem cell (MSC) infusions have recently been suggested to alleviate myocardial injury and ameliorate cardiac function. However, few studies have focused on the effects of MSCs in DCM. Therefore, we explored the effects of MSC-regulated macrophage polarization on myocardial repair in DCM. A DCM rat model was induced by a high-fat diet and streptozotocin (STZ) administration and infused 4 times with MSCs. Rat blood and heart tissue were analyzed for blood glucose levels, lipid levels, echocardiography, histopathology, macrophage phenotype ratios and inflammatory cytokines, respectively. We mimicked chronic inflammation in vitro by inducing peritoneal macrophages with high glucose and LPS, then cocultured these macrophages with MSCs to explore the specific mechanism of MSCs on macrophage polarization. DCM rats exhibited abnormal blood glucose levels and lipid metabolism,
The regulation of macrophage activator protein-1 (AP-1) gene expression by LPS and cytokines is of potentially crucial importance in the pathogenesis of several diseases. The action of LPS and four cytokines on AP-1 gene expression in the murine macrophage J774.2 cell line was, therefore, studied. Exposure of the cells to IL-6 produced no changes in the mRNA levels of all AP-1 members studied. In contrast, the expression of JunB, c-jun and c-fos, but not JunD, was increased by LPS, TNF-α, IFN-γ and IL-1, albeit with different kinetics and magnitude of induction. Electrophoretic mobility shift assays showed a close correlation between the expression of the AP-1 genes and the functional AP-1 DNA binding activity and, additionally, demonstrated the participation of heterodimeric interactions between the different members. These studies provide insights into the potential mechanisms that may be involved in the mediator-specific modulation of AP-1 regulated macrophage gene expression.. ...
Epigenetic control of macrophage differentiation is tissue-specific. Relative to dendritic cells, tissue macrophages poorly present antigens to other immune cells and fail to migrate to regional lymph nodes (22). Transcriptomic profiling of four tissue-resident macrophage populations by the ImmGen consortium revealed that macrophages from different tissues - brain microglia, splenic red pulp macrophages, large peritoneal macrophages, and Kupffer cells in the liver - had more differences in their transcriptional program than similarities (23). In contrast, dendritic cells recovered from a variety of tissues had more similar transcriptomes. These findings suggested that tissue-resident macrophages were uniquely defined by factors originating from their microenvironment. In seminal studies, two groups of investigators used transcriptional and epigenomic profiling of tissue-resident macrophage populations to provide insights into the molecular events that allow monocytes to differentiate along ...
Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that infects alveolar macrophages following aerosol transmission. Lung macrophages provide a critical intracellular niche that is required for Mtb to establish infection in the human host. This parasitic relationship is made possible by the capacity of Mtb to block phagosome maturation following entry into the host macrophage, creating an environment that supports bacillary replication. Apoptosis is increasingly understood to play a role in host defense against intracellular pathogens including viruses, fungi, protozoa and bacteria. In the last 15 years an understanding of the role that macrophage apoptosis plays in TB has begun to emerge. Here we review the history and current state of the art of this topic and we offer a model of the macrophage-pathogen interaction that takes into the account the complexities of programmed cell death and the relationship between various death signaling pathways and host defense in TB.
Macrophage-enriched peritoneal exudate cells from mice infected with Mycobacterium bovis BCG, macrophage-like tumor cells (PU 5-1.8), and peritoneal macrophages propagated in vitro with macrophage growth factor released tumoricidal activity into the culture medium within 2 to 3 h after stimulation with nanogram quantities of bacterial lipopolysaccharide. The cytotoxic activities from each of the macrophage culture supernatants eluted from diethylaminoethyl-Sephacel columns at a sodium chloride concentration of 200 mM exhibited a molecular weight of 50,000 to 60,000 as estimated by gel filtration, were stable at 56 degrees C for 30 min, and were active at a pH range of 6 to 10. A rabbit antiserum directed against serum-derived cytotoxic activity (tumor-necrotizing factor) from BCG-infected and lipopolysaccharide-challenged mice inhibited all of the cytotoxic activities generated in vitro. This suggests that the macrophage-derived cytotoxins are identical with serum-derived cytotoxic factor, which ...
TY - JOUR. T1 - Distinct localization of GLUT-1, -3, and -5 in human monocyte-derived macrophages. T2 - Effects of cell activation. AU - Malide, Daniela. AU - Davies-Hill, Theresa M.. AU - Levine, Mark. AU - Simpson, Ian. PY - 1998/3/1. Y1 - 1998/3/1. N2 - We determined subcellular localization of GLUT-1, GLUT-3, and GLUT-5 as human monocytes differentiate into macrophages in culture, and effects of the activating agents N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol myristate acetate (PMA). Western blot analysis demonstrated progressively increased GLUT-1, rapidly decreased GLUT-3, and a delayed increase of GLUT-5 expression during differentiation. Confocal microscopy revealed that each isoform displayed a unique subcellular distribution and cell-activation response. GLUT-1 was localized primarily to the cell surface but was also detected in the perinuclear region in a pattern characteristic of recycling endosomes. GLUT-3 exhibited predominantly a distinct vesicle-like staining but ...
Figure 6. Accumulation of activated macrophages in tumors following PD-L1 antibody treatment and inhibited tumor growth in Rag−/− mice treated with PD-L1 antibody. B16 melanoma cells were injected into C57Bl/6 mice and the mice were treated with PBS, irrelevant isotype, or PD-L1 antibody. Tumor, spleen, and lymph node tissue was harvested for flow-cytometric analysis of macrophage populations (A) and percentages of tumor macrophages and T cells are shown in B. We also measured surface expression of tumor macrophage MHC II (C) by flow cytometry, and tumor tissues were stained for F4-80 (green) and MHC II (red) expression before counterstaining with DAPI (blue) for imaging at 10× magnification (D). Statistical comparison of cell numbers and expression of surface markers were conducted by two-way ANOVA using Prism7 software. These data are representative of two repeated experiments with four mice in each group. Next, PyMT breast carcinoma cells were injected into Rag−/− mice and the mice ...
Due to the important role of monocytes/macrophages in the pathogenesis of AIDS, potential drugs with anti-HIV activity in lymphocytes must also be effective in monocytes/macrophages. For testing the efficacy of antiviral substances, monocytes/macrophages from peripheral blood were infected, respectively, with highly replicating HIV1 and HIV2 strains, thereby providing an extremely sensitive system of testing. Azidothymidine was found to inhibit both HIV types at 0.04 microgram/ml. The polysulphated polyxylan, Hoe/Bay-946 (MW 6,000 Daltons), which acts through a different mechanism and is being tested in clinical pilot studies in Germany, was also found to be effective against HIV1 and HIV2 in macrophages at concentrations of 10-50 micrograms/ml. ...
Macrophages are heterogenous phagocytic cells with an important role in the innate immunity. They are, also, significant contributors in the adaptive immune system. Macrophages are the most abundant immune cells in the lung during allergic asthma, which is the most common chronic respiratory disease of both adults and children. Macrophages activated by Th1 cells are known as M1 macrophages while those activated by IL-4 and IL-13 are called alternatively activated macrophages (AAM) or M2 cells. AAM are subdivided into four distinct subtypes (M2a, M2b, M2c and M2d), depending on the nature of inducing agent and the expressed markers. IL-4 is the major effector cytokine in both alternative activation of macrophages and pathogenesis of asthma. Thus, the role of M2a macrophages in asthma is a major concern. However, this is controversial. Therefore, further studies are required to improve our knowledge about the role of IL-4-induced macrophages in allergic asthma, through precisive elucidation of the roles
Salmonella induces programmed cell death in macrophages by complex mechanisms that involve distinct pathways and require the bacterial TTSS encoded in the pathogenicity island 1 (SPI-1 TTSS). One death pathway, which results in rapid macrophage death with features of necrosis, is dependent on caspase-1 and the SPI-1 TTSS-secreted protein SipB (Hersh et al., 1999; Brennan and Cookson, 2000; Jesenberger et al., 2000). However, macrophages from caspase-1−/− mice also undergo programmed cell death, although with delayed kinetics and different morphological features. Here, we have described another death pathway induced by Salmonella that is independent of caspase-1. A systematic bacterial genetic analysis led us to conclude that this cell death pathway is also dependent on SipB, a protein with membrane fusion activity that is delivered into host cells by the SPI-1 TTSS. This analysis was complicated by the known dual function of SipB, which acts both as an effector of virulence within cells and ...
Results Patients with lupus display decreased expression of Bim in circulating monocytes and reduced Bim expression in kidney macrophages. CreLysMBimflox/flox mice develop a lupus-like disease that mirrors aged Bim-/- mice including loss of the marginal zone macrophages, splenomegaly, lymphadenopathy, autoantibodies including anti-DNA IgG, and a type I interferon signature as compared to control mice. CreLysMBimflox/flox mice also exhibit increased mortality attributed to immune complex deposition and increased numbers of kidney macrophages all of which contribute to glomerulonephritis. The loss of Bim in macrophages is sufficient to break tolerance as adoptive transfer of wild-type lymphocytes into CreLysMBimflox/floxRag-/- mice leads to systemic autoimmunity. We also identified that the loss of TLR signalling adaptor protein TRIF but not MyD88 is essential for progression to GN phase but is dispensable for systemic autoimmunity. RNA seq analysis of sorted kidney macrophages revealed a novel ...
Results In human PDAC, TAMs predominantly exhibited an immunoregulatory profile, characterised by expression of scavenger receptors (CD206, CD163) and production of interleukin 10 (IL-10). Surprisingly, while the density of TAMs associated to worse prognosis and distant metastasis, CTX restrained their protumour prognostic significance. High density of TAMs at the tumour-stroma interface positively dictated prognostic responsiveness to CTX independently of T-cell density. Accordingly, in vitro, gemcitabine-treated macrophages became tumoricidal, activating a cytotoxic gene expression programme, inhibiting their protumoural effect and switching to an antitumour phenotype. In patients with human PDAC, neoadjuvant CTX was associated to a decreased density of CD206+ and IL-10+ TAMs at the tumour-stroma interface. ...
The regulation of innate immune responses to pathogens occurs through the interaction of Toll-like receptors (TLRs) with pathogen-associated molecular patterns and the activation of several signaling pathways whose contribution to the overall innate immune response to pathogens is poorly understood. We demonstrate a mechanism of control of murine macrophage responses mediated by TLR1/2 heterodimers through c-Jun N-terminal kinase 1 (JNK1) activity. JNK controls tumor necrosis factor alpha production and TLR-mediated macrophage responses to Borrelia burgdorferi, the causative agent of Lyme disease, and the TLR1/TLR2-specific agonist PAM(3)CSK(4). JNK1, but not JNK2, activity regulates the expression of the tlr1 gene in the macrophage cell line RAW264.7, as well as in primary CD11b(+) cells. We also show that the proximal promoter region of the human tlr1 gene contains an AP-1 binding site that is subjected to regulation by the kinase and binds two complexes that involve the JNK substrates c-Jun, ...
The diverse functions of macrophages as participants in innate and acquired immune responses are regulated by the specific milieu of environmental factors, cytokines, and other signaling molecules that are encountered at sites of inflammation. Microarray analysis of the transcriptional response of mouse peritoneal macrophages to the T(H)2 cytokine interleukin-4 (IL-4) identified Ym1 and arginase as the most highly up-regulated genes, exhibiting more than 68- and 88-fold induction, respectively. Molecular characterization of the Ym1 promoter in transfected epithelial and macrophage cell lines revealed the presence of multiple signal transducers and activators of transcription 6 (STAT6) response elements that function in a combinatorial manner to mediate transcriptional responses to IL-4. The participation of STAT6 as an obligate component of protein complexes binding to these sites was established by analysis of nuclear extracts derived from STAT6-deficient macrophages. Macrophage expression of Ym1 was
Macrophages have been found to both promote liver fibrosis and contribute to its resolution by acquiring different phenotypes based on signals from the micro-environment. The best-characterized phenotypes in the macrophage spectrum are labeled M1 (classically activated) and M2 (alternatively activated). Until now the in situ localization of these phenotypes in diseased livers is poorly described. In this study, we therefore aimed to localize and quantify M1- and M2-dominant macrophages in diseased mouse and human livers. The scarred collagen-rich areas in cirrhotic human livers and in CCl4-damaged mouse livers contained many macrophages. Though total numbers of macrophages were higher in fibrotic livers, the number of parenchymal CD68-positive macrophages was significantly lower as compared to normal. Scar-associated macrophages were further characterized as either M1-dominant (IRF-5 and interleukin-12) or M2-dominant (CD206, transglutaminase-2, and YM-1) and significantly higher numbers of both of
Regularly, we identified that host macrophages engulfed alloreactive T cells in between and h of in vitro culture and, as a result, way more effectively than host DC . To examine regardless of whether host macrophages may also engulf donor T cells in vivo, we traced the fate of alloreactive T cells for the duration of the h just after their injection in lethally irradiated recipient mice. Alloreactive T cells accumulated close to the spleen marginal zone shortly after adoptive transfer and steadily shifted toward the T cell area . A substantial amount of donor T cells had been trapped in the red pulp in close contact with host macrophages at early time points after their transfer . Steady with effects obtained in cultures, CFSE labeled donor T cells have been engulfed by splenic macrophages in the course of the 1st day of transplant and ahead of the initiation of donor T cell proliferation in vivo ...
The derivation of human macrophages from peripheral blood monocytes remains a convenient method for the study of macrophage biology. However, for macrophage differentiation, a significant proportion of development has occurred prior to the monocyte stage; monocyte subsets also have varying potential for differentiation. Differentiation of macrophages from a less mature precursor, such as CD34+ haematopoietic stem cells, can further inform with regard to the development of macrophage-lineage cells. CD34+ cells were cultured in serum-free medium containing Flt3L, SCF, IL-3, IL-6 and M-CSF. Using differing combinations of growth factors, the effect on cell proliferation and differentiation to adherent macrophage-like cells was determined. The proliferative response of CD34+ cells to M-CSF was determined during the initial phase of cell culture. Thirteen combinations of SCF, IL-3, IL-6 and M-CSF were then compared to determine the optimum combination for proliferation. Adherence was used to isolate mature
Mouse monoclonal antibody raised against macrophage surface antigen. Native human alveolar macrophages. (MAB1733) - Products - Abnova
Myocardial healing after myocardial infarction (MI) is accomplished by replacement fibrosis in the damaged region, and interstitial fibrosis takes place in the remote areas toward adverse ventricular remodeling. The collagen is produced by myofibroblasts, with infiltrating macrophages further facilitating this process (1,2). Macrophages infiltrate in large numbers at the site of injury after MI in human and in experimental animal models (3). These macrophages aid in the process of myocardial healing and assume multiple roles at different stages, depending on their origin whether infiltrating or resident (3,4). This involves removal of dead necrotic and apoptotic cells, regulation of fibroblast/myofibroblast function, and ultimately, wound resolution. Macrophages and fibroblasts are 2 major cell types involved in myocardium healing, and often lead to adverse myocardial remodeling and fibrosis (1,2,5).. It is well established that differentiated cells in various circumstances change their ...
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about 21 micrometres (0.00083 in) in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense (innate immunity) as well as help initiate specific defense mechanisms (adaptive immunity) of vertebrate animals. Their role is to phagocytose (engulf and then digest) cellular debris and pathogens, either as stationary or as mobile cells. They also stimulate lymphocytes and other immune cells to respond to pathogens. They are specialized phagocytic cells that attack foreign substances, infectious Microbes and cancer cells through destruction and ingestion. Macrophages can be identified by specific expression of a number of proteins including CD14, CD11b, F4/80 (mice)/EMR1 (human), Lysozyme M, MAC-1/MAC-3 and CD68 by flow cytometry or immunohistochemical staining. They move by action of Amoeboid movement.
Lung macrophages (LMϕs) play a key role in pulmonary innate immunity. They polarize into different phenotypes adapting to the needs of the immediate pulmonary environment. Studies in our laboratory suggest that murine LMϕs are endowed with an autocrine gamma-aminobutyric acid (GABA) signaling system. My honors thesis study found that antagonizing the autocrine GABA signaling in alveolar macrophages (AMϕs) increased secretion of the M1 cytokine tumor necrosis factor-alpha (TNF-α), suggesting a role for GABA signaling in immune response. This project explored whether GABA signaling plays a role in LMϕ polarization. Results from this study confirmed that bacterial toxin lipopolysaccharide (LPS) and the Th1 cytokine interferon gamma (IFNγ) shifted LMϕs to the pro-inflammatory M1 phenotype, marked by increased expression of inducible nitric oxide synthase (iNOS). On the other hand, the Th2 cytokines interleukin (IL)-4 and IL-13 shifted LMϕs toward the M2 phenotype marked by increased arginase-1.
TY - JOUR. T1 - Intrinsic and extrinsic factors in muscle aging. AU - Cannon, Joseph G.. PY - 1998/1/1. Y1 - 1998/1/1. N2 - The regenerative potential of skeletal muscle, and overall muscle mass, decline with age. This regenerative potential may be influenced by autocrine growth factors intrinsic to the muscle itself. Extrinsic host factors that may influence muscle regeneration include hormones, growth factors secreted in a paracrine manner by accessory cells, innervation, and antioxidant mechanisms. Unaccustomed exercise, which involves mechanical overload of myofibers, provides a convenient method for studying muscle regeneration in both humans and animal models. An inflammatory response ensues in which distinctive populations of macrophages infiltrate the affected tissue: some of these macrophages are involved in phagocytosis of damaged fibers; other macrophages arriving at later times may deliver growth factors or cytokines that promote regeneration. These include fibroblast growth factor ...
Monocytes, macrophages and dendritic cells (DCs) are developmentally related regulators of the immune system that share the monocyte-macrophage DC progenitor (MDP) as a common precursor. Unlike differentiation into DCs, the distal pathways for differentiation into monocytes and monocyte-derived macrophages are not fully elucidated. We have now demonstrated the existence of a clonogenic, monocyte- and macrophage-restricted progenitor cell derived from the MDP. This progenitor was a Ly6C+ proliferating cell present in the bone marrow and spleen that generated the major monocyte subsets and macrophages, but not DCs or neutrophils. By in-depth quantitative proteomics, we characterized changes in the proteome during monocyte differentiation, which provided insight into the molecular principles of developing monocytes, such as their functional maturation. Thus, we found that monocytes and macrophages were renewed independently of DCs from a committed progenitor ...
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In this study, we sought to determine whether CX3CL1 and CCR2 act independently or in concert to promote lesion formation through their effects on macrophage accumulation. There are 2 major findings in the present study. First, although deletion of either CX3CL1 or CCR2 reduced macrophage presence and atherosclerosis, atheroprotection in the CCR2−/− mice was more robust. Second, there was an even greater reduction of lesion formation in the CX3CL1−/− CCR2−/− double knockouts, which suggests that CX3CL1 and CCR2 have independent functions in recruiting monocyte/macrophages. These differences, which were not linked to changes in cholesterol levels or lipoprotein profiles, provide mechanistic insights into the role of monocyte chemoattractants in fatty streak formation and early plaque development.. The past 2 decades have witnessed a rapid increase in our understanding of leukocyte migration throughout the body, with the identification of ≈50 chemokines and ,20 chemokine receptors. ...
RNA interference is an evolutionary conserved immune response mechanism that can be used as a tool to provide novel insights into gene function and structure. The ability to efficiently deliver small interfering RNA to modulate gene expression in vivo may provide new therapeutic approaches to currently intractable diseases. In vitro, siRNA targeting IL-12p40 was delivered to the murine macrophage cell line (J774A.1) encapsulated in a liposome with an IL-12 inducing agent (LPS/IFN-γ) over a number of time points. Controls included a variety of non-target specific siRNA reagents. Supernatants were analyzed for cytokine production while the cells were removed for mRNA profiling. In vivo, siRNA-targeting IL-12p40 was delivered to the murine peritoneal cavity in a therapeutic fashion, after endotoxin (LPS) challenge. Cells from the peritoneal cavity were removed by lavage and analyzed by flow cytometry. Levels of IL-12 present in lavage and in serum were also examined by ELISA. In this report, we show that
Persistent, unresolved inflammation in the liver represents a key trigger for hepatic injury and fibrosis in various liver diseases and is controlled by classically activated proinflammatory macrophages, while restorative macrophages of the liver are capable of reversing inflammation once the injury trigger ceases. Here we exhibit neutrophils as key contributors to resolving the inflammatory response in the liver using two models of liver inflammation resolution. Using two models of liver inflammatory resolution, we found that mice undergoing neutrophil depletion during the resolution phase exhibited unresolved hepatic inflammation, activation of the fibrogenic machinery, and early fibrosis. These findings were associated with an impairment of the phenotypic switch of proinflammatory macrophages into a restorative stage after removal of the cause of injury and an increased NLRP3/miR-223 ratio. Mice with a deletion of the granulocyte-specific miR-223 gene showed a similarly impaired resolution ...
...For those coping with Crohns disease a new research report published... By increasing the knowledge on the different macrophage subsets in th...To make this discovery scientists studied blood and intestinal biopsy...,Scientists,discover,the,specific,types,of,macrophages,that,affect,Crohns,disease,severity,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
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TY - JOUR. T1 - Intracellular bacteria recognition contributes to maximal interleukin (IL)-12 production by IL-10-deficient macrophages. AU - Naruse, H.. AU - Hisamatsu, T.. AU - Yamauchi, Y.. AU - Chang, J. E.. AU - Matsuoka, K.. AU - Kitazume, M. T.. AU - Arai, K.. AU - Ando, S.. AU - Kanai, Takanori. AU - Kamada, N.. AU - Hibi, T.. PY - 2011/4. Y1 - 2011/4. N2 - Interleukin (IL)-12 is a key factor that induces T helper cell type 1-mediated immunity and inflammatory diseases. In some colitis models, such as IL-10 knock-out (KO) mice, IL-12 triggers intestinal inflammation. An abundant amount of IL-12 is produced by intestinal macrophages in response to stimulation by commensal bacteria in IL-10 KO mice. Intact bacteria are more potent inducers of macrophage IL-12 production than cell surface components in this model. This suggested that cell surface receptor signalling and intracellular pathogen recognition mechanisms are important for the induction of IL-12. We addressed the importance of ...
Definition of macrophage colony stimulating factor in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is macrophage colony stimulating factor? Meaning of macrophage colony stimulating factor as a legal term. What does macrophage colony stimulating factor mean in law?
There are comments on PubPeer for publication: In vitro -induced M2 type macrophages induces the resistance of prostate cancer cells to cytotoxic action of NK cells (2018)
Background Estimating the mandatory dose in radiotherapy can be of crucial importance because the administrated dose ought to be sufficient to eliminate the tumor and at the same time should inflict minimal harm on normal cells. Outcomes We derive a precise phase-diagram for the steady-state TCP from the display and model that at high, clinically-relevant dosages of rays, the differentiation between energetic and quiescent tumor cells (i.e. accounting for cell-cycle Mouse monoclonal antibody to TAB1. The protein encoded by this gene was identified as a regulator of the MAP kinase kinase kinaseMAP3K7/TAK1, which is known to mediate various intracellular signaling pathways, such asthose induced by TGF beta, interleukin 1, and WNT-1. This protein interacts and thus activatesTAK1 kinase. It has been shown that the C-terminal portion of this protein is sufficient for bindingand activation of TAK1, while a portion of the N-terminus acts as a dominant-negative inhibitor ofTGF beta, suggesting that this ...
Macrophages. Coloured scanning electron micrograph (SEM) of active macrophage cells. In the active state the cell surfaces appear frilly and these frills spread out as projections to draw the cells along the substrate as they seek and engulf particles. Wandering macrophages are monocyte white blood cells from circulating blood that defend the body against invasion by foreign organisms. Macrophages migrate to tissues such as the lymphatic system and lungs. Some types migrate to sites of infection to prevent bacteria taking hold. Macrophages can also detect foreign subst- ances at the initial stage of the bodys immune response. Magnification: x1,500 at 6x7cm size. x5000 at 8x10 inch size. - Stock Image P276/0132
Macrophages are mononuclear phagocytes that play a central role in tissue development and homeostasis, and protecting the organism from infection. Our laboratory is interested in describing the properties of tissue-resident human macrophages and how their properties change throughout life, using modern technologies such as advanced flow cytometry and single cell RNA sequencing. This project aims to describe the properties of placental macrophages and the role they play in anti-viral fetal defense.. Recent Publications. McGovern N, Shin A, Low G, Low D, Duan K, Yao LJ, Msallam R, Low I, Shadan NB, Sumatoh HR, Soon E, Lum J, Mok E, Hubert S, See P, Kunxiang EH, Lee YH, Janela B, Choolani M, Mattar CNZ, Fan Y, Lim TKH, Chan DKH, Tan KK, Tam JKC, Schuster C, Elbe-Bürger A, Wang XN, Bigley V, Collin M, Haniffa M, Schlitzer A, Poidinger M, Albani S, Larbi A, Newell EW, Chan JKY, Ginhoux F. Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2. Nature. 2017 Jun ...
In this study, the human leukemic monocyte lymphoma cell line U-937 was used as an in vitro model for monitoring monocyte/macrophage differentiation. Phorbol 12- myristate (13) (PMA) was used to activate U-937 cells into macrophage-like cells (M0). After 24 hours of PMA treatment, non- adherent U-937 cells became tightly adherent to the culture plates forming M0 cells. M0 cells were then polarized into the M1 macrophage phenotype by treatment with LPS and IFN-γ for another 24 hours. Each of the cytokines IL-4, IL-13, or IL-10 was applied separately to three M0 cultures for 24 hours to induce the M2 macrophage phenotype. M1 and M2 phenotypes displayed distinct morphological characteristics. M1 cells appeared large, with cellular processes (pseudopodia), and intracellular vacuoles while the M2 cells large aggregated into large masses. The undifferentiated U--937 cells expressed less CD206 and CD86 but greater amounts of CD163, CD80, and CD200R than did the differentiated U937 cells (M0 macrophages).
Schroit, A; Geiger, B; and Gallily, R, "The capacity of macrophage components to inhibit anti-macrophage serum activity." (1973). Subject Strain Bibliography 1973. 2291 ...
Despite the extensive studies in the past two decades and the development of a generic cell migration model, composed of cell adhesion, detachment, and receptor recycling (Stossel, 1994; Murphy and Gavrilovic, 1999; Sanchez‐Madrid and del Pozo, 1999; Webb et al, 2002), the extracellular events that orchestrate temporally and spatially the transition among these individual steps are unknown. Moreover, evidence for a critical role of macrophage emigration to the lymph nodes in inhibiting the progression of atherosclerosis is emerging (Libby, 2002; Llodra et al, 2004). However, the mechanism that controls their emigration, especially under activated conditions, remains elusive. In this work, we explored the mechanism by which activated macrophages migrate within an inflammatory environment using genetic and biochemical approaches. Our data reveal that deletion of the PAI‐1, tPA, LRP, and Mac‐1 genes all impair the ability of macrophages to migrate from the peritoneal cavity in response to ...
Macrophages play an important role in immune and non-immune defence mechanisms. They form a first line of defence against bacterial, viral and other forms of microbiological contamination penetrating into the bodies of vertebrates. Macrophages are large cells, found in almost all bodily tissues where they can have varying forms and names (e.g. Kupffer cells, alveolar macrophages, microglia, osteoclasts, red pulp macrophages). Macrophages "scavenge", they ingest and digest all foreign substances, microbes, cancer cells and cellular debris that might be potential pathogens. This process is called phagocytosis. Macrophages further regulate functions of many non-phagocytic cells, mainly through mediation of soluble molecules such as cytokines and chemokines. They are involved in innate immunity, adaptive immunity and can have (anti-) inflammatory effects.. Liposomes are artificially prepared spheres and consist of concentric phospholipid bilayers. When phospholipids are dispersed in water, the ...
The most abundant immune cell types of the tumor microenvironment macrophages recruited there by tumor-eluted factors. The role of these immune cells in tumor progression, and the interplay between tumor and immune cells is an emerging field of research with potential for novel treatment strategies. Here, a TIE2 expressing macrophage (TEM) subtype is integrated into a virtual tumor model. Within the 2D microenvironment, the TEM will differentiate from an extravasated monocyte precursor, congregate around the abluminal side of the vasculature in response to a chemoattractant gradient, secrete cytokines which favor differentiation of a separate angiogenic macrophage subtype [1]. The effects of macrophage populations on tumor progression on angiogenic activity and tumor growth will be examined.
AFIK we do not know exactly why activated macrophages express substantially increased FR beta receptors. This is further complicated by the notion of polarized macrophages as well as a number of different macrophage phenotypes (which can be changed by signaling from one the same macrophage) that are considered proinflammatory and anti inflammatory. I have questioned experts in the field since I am working on a folate receptor conjugate that can be used to externally image macrophages in atheroma , potentially stratifying fibrous from vulnerable plaques. They do not know why FR beta is expressed or whether someone on folate supplemation is exacerbating or reducing risk. Cold folate will partially block the affinity of receptors for conjugated folate used in imaging. However, FR beta is considered a Trojan horse for the introduction of drugs for diagnosis and therapy of macrophage laden plaques. The kind that want to cause big trouble. I read that folate also affects the production of ROS in ...
AFIK we do not know exactly why activated macrophages express substantially increased FR beta receptors. This is further complicated by the notion of polarized macrophages as well as a number of different macrophage phenotypes (which can be changed by signaling from one the same macrophage) that are considered proinflammatory and anti inflammatory. I have questioned experts in the field since I am working on a folate receptor conjugate that can be used to externally image macrophages in atheroma , potentially stratifying fibrous from vulnerable plaques. They do not know why FR beta is expressed or whether someone on folate supplemation is exacerbating or reducing risk. Cold folate will partially block the affinity of receptors for conjugated folate used in imaging. However, FR beta is considered a Trojan horse for the introduction of drugs for diagnosis and therapy of macrophage laden plaques. The kind that want to cause big trouble. I read that folate also affects the production of ROS in ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the class A macrophage scavenger receptors, which include three different types (1, 2, 3) generated by alternative splicing of this gene. These receptors or isoforms are macrophage-specific trimeric integral membrane glycoproteins and have been implicated in many macrophage-associated physiological and pathological processes including atherosclerosis, Alzheimer's disease, and host defense. The isoforms type 1 and type 2 are functional receptors and are able to mediate the endocytosis of modified low density lipoproteins (LDLs). The isoform type 3 does not internalize modified LDL (acetyl-LDL) despite having the domain shown to mediate this function in the types 1 and 2 isoforms. It has an altered intracellular processing and is trapped within the endoplasmic reticulum, making it unable to perform endocytosis. The isoform type 3 can inhibit the function of isoforms type 1 and ...
A recent study proposes a novel role for inhibitory guidance cues in regulating macrophage trafficking during atherosclerosis.1 The study authors demonstrate that Netrin-1, a laminin-related protein with a previously established role in axon migration and tumorigenesis, contributes to atherosclerosis by preventing the emigration of macrophages from plaque.. Monocyte recruitment to areas of subendothelial lipid deposition has long been identified as a critical early step in the inflammatory pathophysiology of atherosclerosis.2,3 Less is known, however, about the signals that mediate both the retention and efflux of macrophages from atherosclerotic lesions. Evidence from prior studies has suggested that lipid accumulation promotes the retention of macrophages in atherosclerotic lesions by disrupting CCR7-dependent chemotaxis, which under normal conditions enhances macrophage efflux from sites of inflammation.4-6 Other studies have shown that inhibitory guidance cues mediated by the laminin-related ...
Macrophage engulfing bacteria http://bit.ly/1HAcwgY Macrophages are a type of white blood cells essential for the human immune system to protect the body against foreign substances such as virus and bacteria. They also play a crucial role in tissue homeostasis and can contribute to tumor growth and chronic inflammatory diseases such as diabetes, obesity etc. Macrophages are therefore potential drug targets and there is a growing interest in understanding these white blood cells.. The prevailing dogma states that macrophages are produced from monocytes generated in the bone marrow from adult hematopoietic stem cells. However, scientists from the Singapore Immunology Network (SIgN), a research institute under the Agency for Science, Technology and Research (A*STAR), Singapore have shed some light on the origin of adult tissue macrophages. The work was published in the prestigious scientific journal Immunity.. A team of scientists led by Dr. Florent Ginhoux, Principal Investigator of SIgN, ...
Macrophages make an antiviral protein called SAMHD1, which prevents HIV from replicating in these cells - except for when the protein is switched off, as part of a natural process discovered by the UCL-led team.. "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. "And yet we found theres a window of opportunity when SAMHD1 is disabled as part of a regularly-occurring process in macrophages.". Lead author of the EMBO Journal study, Dr Petra Mlcochova (UCL Infection & Immunity) said: "Other viruses can disable SAMHD1, but HIV cannot. Our work explains how HIV can still infect macrophages, which are disabling SAMHD1 by themselves.". The reason why SAMHD1 gets switched off remains to be determined, but the authors suggest it might be done in order to repair damaged DNA, part of the normal functioning ...
The global burden of chronic kidney diseases remains an ongoing medical challenge. Therapies that can halt or reverse advanced renal injury are not yet available. Increasing numbers of patients progress to the end-stage renal failure and require renal replacement therapy, the latter being associated with significant mortality, a lower quality of life, and high costs for national health systems. Thus, new treatment strategies that slow down, halt or even revert progressive renal damage are requested. Chemokines and their receptors are involved in the pathogenesis of renal diseases. They mediate leukocytes and macrophages recruitment and activation during initiation as well as progression of renal inflammation. Infiltrating leukocytes are the major source for proinflammatory and profibrotic cytokines and are therefore critical for mediating fibroblast proliferation, differentiation into myofibroblasts, matrix production, and tubular atrophy. Recent advances in the understanding of the molecular ...
People with diabetes are at increased risk for atherosclerosis and have high CVD morbidity and mortality rates. Tools for detecting and quantifying atherosclerotic pro/regression in people with diabetes and other CVD risk factors lack sensitivity and specificity for molecular level events that occur during the early stages of atherogenesis. Inflammatory macrophage infiltration in the vessel endothelium is an early, molecular level proatherogenic event. Activated macrophages consume glucose at a high rate. Novel in vivo radiotracer PET/CT techniques have been developed to detect, image and quantify molecular level events like macrophage inflammation and glucose utilization (18FDG) in human vessels. We propose to develop and test this novel technique in the Center for Clinical Imaging Research (CCIR) at WUMS. We propose that HIV-infected people with significant CVD risk profiles are a suitable, unique human model for testing these novel imaging techniques. HIV-infected people taking anti-HIV ...
Integrative genomics gets the potential to discover relevant loci, as scientific outcome and response to chemotherapies are likely not because of an individual gene (or data type) but instead a complicated relationship involving hereditary variation, mRNA, DNA methylation, and duplicate number variation. the knockdown of and led to CDDP level of resistance in multiple cancers cell lines. This research demonstrates the tool of the integrative GS evaluation strategy for discovering novel genes connected with response to cancers therapies, moving nearer to customized therapy decisions for cancers patients. Launch Platinum agents, such as for example cisplatin (CDDP), are generally used in the treating a number of malignancies, including ovarian and lung malignancies. Nevertheless, response to therapy varies among sufferers. One of the primary challenges to attain desirable therapeutic results is the huge inter-patient deviation in scientific response and toxicity. Main molecular mechanisms root ...
Macrophage polarization review exploring the function and phenotype of M1, M2, TAM, TCR+, CD169+ macrophages, plus comparisons between mouse and human macrophages
This necessity for prolonged contact may prove to be important for macrophage activation. This is suggested by comparing the prolonged effects in vivo of injection of casein, on the one hand, and C. parvum or other anaerobic coryneforms on the other. Both have short-term stimulating effects on macrophages. Both casein and C. parvum are chemotactic for macrophages and both induce a macrophage exudate 2-5 days after injection into the peritoneal cavity of the guinea-pig (49). However after casein-induction, these macrophages disappear from the peritoneal cavity soon afterwards. The relevance of this mechanism to the microbicidal effect of activated macrophages is not known, especially since mature macrophages, at least in the mouse, are thought to be relatively poor in peroxidase activity (25). 2. Nonmicrobial Targets Activated macrophages appear to kill tumor cells by a nonphagocytic mechanism. Several authors have emphasized the need for a close contact between activated macrophages and target ...
The Institute of Pharmacology and Structural Biology (www.ipbs.fr) has an open postdoctoral position to work on podosomes, cell structures involved in adhesion, matrix proteolysis, mechanosensing and cell migration in 3D environments (1-9). Macrophage tissue infiltration plays beneficial roles in protective immunity and detrimental roles in several diseases. Tissue infiltrated macrophages favor the progression of e.g. most cancers and chronic inflammations. Therefore, it is a challenging issue to control macrophage migration as a new therapeutic strategy.. Our team has reported that podosomes are instrumental in the protease-dependent 3D migration of macrophages. To progress in the knowledge of this cell structure, we developed a method called Protrusion Force Microscopy (3,10,11) and we used STORM-SAF microscopy (12) that allowed drawing a preliminary picture of the podosome architecture which explains the generation of protrusive force (13). Now, we plan to further characterize the ...
Introduction Methotrexate (MTX) induces macrophage apoptosis in vitro, but there is not much evidence for increased synovial macrophage apoptosis in MTX-treated patients. Macrophage apoptosis is...
In HIV-infected macrophages, newly formed progeny virus particles accumulate in intracellular plasma membrane-connected compartments (IPMCs). Although the virus is usually seen in these compartments, it is unclear whether HIV assembly is specifically targeted to IPMCs or whether some viruses may also form at the cell surface but are not detected, as particles budding from the latter site will be released into the medium. To investigate the fidelity of HIV-1 targeting to IPMCs compared to the cell surface directly, we generated mutants defective in recruitment of the Endosomal Sorting Complexes Required for Transport (ESCRT) proteins required for virus scission. For mutants unable to bind the ESCRT-I component Tsg101, HIV release was inhibited and light and electron microscopy revealed that budding was arrested. When expressed in human monocyte-derived macrophages (MDM), these mutants formed budding-arrested, immature particles at their assembly sites, allowing us to capture virtually all of the virus
Sigma-Aldrich offers abstracts and full-text articles by [Simone Merlin, Kuldeep K Bhargava, Gabriella Ranaldo, Diego Zanolini, Christopher J Palestro, Laura Santambrogio, Maria Prat, Antonia Follenzi, Sanjeev Gupta].
Large collection of high quality biology pictures, photos, images, illustrations, diagrams and posters on marine biology, cell biology, microbiology... for educational purposes.. ...
Materials and methods Cultures of human THP-1 were activated to macrophages by interferon γ (IFNγ) (500 U/ml) and treated for 24 h with calcitriol (10−8M) and 17β-estradiol (E2, 10−8M) alone and in combination.Untreated macrophages (THP-1-activated) were used as controls (cnt). P450-aromatase synthesis was evaluated by immunocytochemistry (ICC) and western blotting (WB), whereas the expression of the related CYP19A1 gene was quantified by Real-Time PCR (RT-PCR). IL-1β, IL-6 and TNFα synthesis was analysed by enzyme immunoassay (ELISA) and WB. The signal transduction pathway of mitogen activated proteins ERK1/2 was evaluated by WB.. ...
Macrophages are major constituents of the microenvironment in many cancers, promoting carcinogenesis, malignant progression and resistance to therapy making them attractive targets for therapeutic intervention. Macrophage Pharmas approach is to manipulate tumour associated macrophages to inhibit the immunosuppression that they generate, leading to more effective anti-tumour immune responses. Esterase Sensitive Motif™ technology represents a strategy of highly selective delivery of small molecule inhibitors to tumour macrophages such that the function of other important anti-tumour immune cells is not impacted. Macrophage Pharma believes that development of these highly novel therapeutics will lead to optimal anti-tumour macrophage activities providing maximal therapeutic responses.. ...
Definition of macrophage processing in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is macrophage processing? Meaning of macrophage processing as a finance term. What does macrophage processing mean in finance?
Properties emerge from the dynamics of large-scale molecular networks that are not discernible at the individual gene or protein level. Mathematical models - such as probabilistic Boolean networks - of molecular systems offer a deeper insight into how these emergent properties arise. Here, we introduce a non-linear, deterministic Boolean model of protein, gene, and chemical interactions in human macrophage cells during HIV infection. Our model is composed of 713 nodes with 1583 interactions between nodes and is responsive to 38 different inputs including signaling molecules, bacteria, viruses, and HIV viral particles. Additionally, the model accurately simulates the dynamics of over 50 different known phenomena, including molecular events associated with viral infection, endocytosis, transport, replication, budding, and cellular release. Statistical analyses of the model reveal network components with significant potential to influence molecular systems in both normal and infected macrophages, many of
Anti-Macrophage Inflammatory Protein 1 alpha / CCL3 antibody (ab32609) has been cited in 1 publications. Find out more about the references
Due to the role of macrophages in immune reactions and the concept of M1/M2 programming and Th1/Th2 paradigm alveolar macrophages (AM) phenotype greatly influence immune response disorders in the lungs.Objective: assessment of immune response functional phenotype imbalance and AM phenotype in COPD.Methods: Generalized analysis of AM phenotype and functional phenotype of immune response was performed by flow cytometry (Beckman Coulter FC500) by expression of M1/M2 AM phenotypes CD markers (CD25, CD80/CD163, CD206, respectively) and cytokine production of proinflammatory M1, anti-inflammatory M2 and M1/M2 cytokines in culture medium (CM) of AM and bronchoalveolar lavage fluid (BALF) in patients with stage 1-3 COPD (1: n=12, 2: n=15, 3: n=14; 32-60 y.o.) and healthy volunteers (HV) (n=10, 35-58 y.o.).Results: M1/M2 ratio of AM CD markers expression progressively increased from stage 1 to 3 COPD (2.6, 3.2 and 4.0 times, respectively, p,0.05) as compared to HV. In stage 1-3 COPD M1/M2 indices of CM ...
Macrophages are important cells at the front-line of immunity where one of their main roles is to release anti-bacterial proteins. We will study the macrophage molecules, subcellular organelles and pathways that help to release these proteins to kill backteria and fight infection. Our studies will identify new cellular targets for boosting immunity and treating inherited diseases with defective macrophage function ...
Phagocytosis. One common way your immune system destroys antigens is by phagocytosis. Phagocytosis is the process of engulfing (or "eating") antigens and releasing enzymes that break down the foreign agent. Some phagocytes, like macrophages, constantly circulate throughout your body, while others remain stationary in certain organs, waiting to be activated. Macrophages scavenge for invaders and escalate your immune systems attack to other white blood cells. When a macrophage consumes an antigen, it displays the antigen to B and T cells so that they, in turn, can initiate an immune response to the foreign agent. For this reason, macrophages are also called antigen-presenting cells. Immune Response. When an antigen makes it past your skin, which is your bodys first line of defense, it will be met with a comprehensive attack. First, macrophages recognize the pathogen, engulf it, and secrete chemicals that tell helper T cells to prepare for action. Helper T cells recognize the invaders shape and ...
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?
Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163+ cells were significantly increased based on the pathological grade. CD163+ cells were
TY - JOUR. T1 - Recombinant human macrophage colony-stimulating factor in nonhuman primates. T2 - Selective expansion of a CD16+ monocyte subset with phenotypic similarity to primate natural killer cells. AU - Munn, David H.. AU - Bree, Andrea G.. AU - Beall, Arthur C.. AU - Kaviani, Michelle D.. AU - Sabio, Hernan. AU - Schaub, Robert G.. AU - Alpaugh, R. Katherine. AU - Weiner, Louis M.. AU - Goldman, Samuel J.. PY - 1996/8/15. Y1 - 1996/8/15. N2 - The CD16 receptor (FcγR-III) is found on many tissue macrophages (Mφs), but its expression on circulating monocytes is restricted to a small, phenotypically distinct subset. The number of these CD16+ monocytes may be markedly increased in response to sepsis, human immunodeficiency virus infection, or metastatic malignancy. We have recently shown that the CD16+ monocyte population is selectively expanded by administration of recombinant human macrophage colony-stimulating factor (rhM-CSF). In the current study, we used the highly rhM-CSF-responsive ...
TY - JOUR. T1 - β2-Agonist clenbuterol suppresses bacterial phagocytosis of splenic macrophages expressing high levels of macrophage receptor with collagenous structure. AU - Shirato, Ken. AU - Sato, Shogo. AU - Sato, Madoka. AU - Hashizume, Yoko. AU - Tachiyashiki, Kaoru. AU - Imaizumi, Kazuhiko. PY - 2013/3. Y1 - 2013/3. N2 - Splenic marginal zone macrophages expressing macrophage receptor with collagenous structure (MARCO) contribute to the clearance of blood-borne pathogens. We determined a splenic adherent cell fraction abundantly containing cells expressing a higher level of MARCO by flow cytometry, and examined the effects of daily administration of an anabolic dose of β2-agonist clenbuterol on the phagocytic capacity of the cells in mice. After 6 weeks of clenbuterol (1.0 mg/kg body weight/d) or vehicle administration to the mice, splenic adherent cells were isolated. These cells were separated into three cell-size subpopulations. Among them, the small-cell subpopulation contained ...
Triamcinolone acetonide (TA) is used for osteoarthritis management to reduce pain, and pre-clinical studies have shown that TA limits osteophyte formation. Osteophyte formation is known to be facilitated by synovial macrophage activation. TA injections might influence macrophage activation and subsequently reduce osteophytosis. Although widely applied in clinical care, the mechanism through which TA exerts this effect remains unknown. In this animal study, we investigated the in vivo effects of TA injections on macrophage activation, osteophyte development and joint degeneration. Furthermore, in vitro macrophage differentiation experiments were conducted to further explain working mechanisms of TA effects found in vivo. Osteoarthritis was induced in rat knees using papain injections and a running protocol. Untreated and TA-treated animals were longitudinally monitored for 12 weeks with in vivo micro-computed tomography (μCT) to measure subchondral bone changes. Synovial macrophage activation was
Looking for online definition of macrophage colony-stimulating factor in the Medical Dictionary? macrophage colony-stimulating factor explanation free. What is macrophage colony-stimulating factor? Meaning of macrophage colony-stimulating factor medical term. What does macrophage colony-stimulating factor mean?
misc{7862195, abstract = {Acute or chronic inflammation in the prostate is implicated in pathogenesis of benign prostate hyperplasia (BPH) as well as development of prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa). Chronic prostatitis (inflammation in the prostate) is associated with high morbidity and negatively impacts life quality. Macrophages are critical regulators of inflammatory processes and are early immune cells responders. Among macrophage-associated genes, the stress-induced enzyme heme oxygenase-1 (HO-1), which degrades heme to carbon monoxide (CO), biliverdin and iron, has strong immunomodulatory effects in in vitro and in vivo disease models. In this study, we investigated the specific role of HO-1 in macrophages on modulation of prostate inflammation. We established a mouse model of bacterial prostatitis in wild type mice, and evaluated the role of HO-1 in pathogen-induced prostate inflammation by using mice with conditional deletion of HO-1 in myeloid cells ...
1. Still GF. On a form of chronic joint disease in children. Med Chir Trans 1897; 80: 47. 2. Bywaters EG. Stillęs disease in the adult. Ann Rheum Dis 1971; 30: 121. 3. Yamaguchi M, Ohta A, Tsunematsu T. Preliminary criteria for classification of adult Stillęs disease. J Rheumatol 1992; 19: 424-430. 4. Deane S, Selmi C, Teuber SS, Gershwin ME. Macrophage Activation Syndrome in Autoimmune Disease. Int Arch Allergy Immunol 2010; 153: 109-120. 5. Sawhney S, Woo P, Murray KJ. Macrophage activation syndrome: A potentially fatal complication of rheumatic disorders. Arch Dis Child 2001; 85: 421-426. 6. Behrens EM, Beukelman T, Paessler M, Cron RQ. Ocult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis. J Rheumatol 2007; 34: 1133-1138. 7. Parodi A, Davi S, Pringe AB, Pistorio A, Ruperto N, Magn-manzoni S, et al. Macrophage Activation syndrome in Juvenile Systemic Lupus Erythematosus. Arthritis Rheum 2009; 60(11): 3388-3399. 8. Athreya BH. Is macrophage activation ...
Preoperative oral treatment with lactulose is used to prevent complications after surgery in patients with obstructive jaundice. The effect is perhaps the result of an inactivation of gut derived endotoxins but the exact mechanism of action is, however, unknown. Tumour necrosis factor is an important mediator of endotoxin toxicity. The cytokine tumour necrosis factor is mainly produced by mononuclear phagocytes. In this study, the effect of lactulose on the endotoxin induced tumour necrosis factor release by monocytes was investigated. The direct effect of lactulose on endotoxin was tested in a chromogenic limulus amoebocyte lysate assay. Polymyxin B a known inactivator of endotoxin was used as control in both experiments. Lactulose has a limited capacity to inactivate endotoxin as measured in the endotoxin assay. In contrast lactulose significantly reduced endotoxin induced tumour necrosis factor production by monocytes. In conclusion lactulose inhibits tumour necrosis factor production by a ...
Macrophages[edit]. In the macrophage, the primary signal for activation is IFN-γ from Th1 type CD4 T cells. The secondary ... As a result, the macrophage expresses more CD40 and TNF receptors on its surface, which helps increase the level of activation ... The activated macrophage can then destroy phagocytosed bacteria and produce more cytokines. ... macrophages, basophils, NK cells, B lymphocytes, as well as non-haematopoietic cells (smooth muscle cells, endothelial cells, ...
Nonspecific recognition by macrophages[edit]. For more details on Toll-like receptors, see Pattern recognition receptors. ... Macrophages and related cells employ a different mechanism to recognize the pathogen. Their receptors recognize certain motifs ... After recognizing an antigen, an antigen presenting cell such as the macrophage or B lymphocyte engulfs it completely by a ... expressed by the macrophages.[1][17] Since the same receptor could bind to a given motif present on surfaces of widely ...
"Pulmonary macrophages". European Respiratory Journal. 7 (9): 1678-1689. doi:10.1183/09031936.94.07091678. PMID 7995399. "goblet ...
M1 macrophages. ILC1 also recruit DC and cytotoxic T cells. On the other hand, IFN g and TNF a play important role in induction ...
Reactive diseases of macrophages *Hemophagocytic syndrome - a condition where macrophages phagocytose myeloid and erythroid ... The source for histiocytes is the monocyte/macrophage line. Monocytes (found in the blood) and macrophages (found in tissue) ...
... and peritoneal macrophages. Pathogen-induced necrosis programs in cells with immunological barriers (intestinal mucosa) may ...
Other cells that contain haemoglobin include the A9 dopaminergic neurons in the substantia nigra, macrophages, alveolar cells, ... hemoglobin has non-oxygen-carrying functions as an antioxidant and a regulator of iron metabolism in macrophages,[102] alveolar ... they are removed from the circulation by the phagocytic activity of macrophages in the spleen or the liver or hemolyze within ... which is exclusively expressed on monocytes or macrophages. Within these cells the hemoglobin molecule is broken up, and the ...
Macrophage, CD8+ T cell. B-cell, eosinophil, mast cell Cytokines produced. interferon-γ and TNF-β. Interleukin-2 interleukin-10 ... The fragment is presented to it by MHC2.[13] IFN-γ, interferon γ; TGF-β, transforming growth factor β; mø, macrophage; IL-2, ... HIV mainly targets lymphoid CD4+ T cells, but can infect other cells that express CD4 such as macrophages and dendritic cells ( ... CD4+ T cells can also stimulate cells such as natural killer cells and macrophages via cytokines such as interferon-gamma, ...
This attracts more macrophages. In some regions of increased macrophage activity, macrophage-induced-enzymes erode away the ... Once inside, they transform into macrophages which will ingest the oxidized lipoprotein particles. The macrophages sometimes ... A vulnerable plaque is a kind of atheromatous plaque - a collection of white blood cells (primarily macrophages) and lipids ( ... Researchers have found that accumulation of white blood cells, especially macrophages, termed inflammation, in the walls of the ...
... mannose receptor of macrophages; 180 Kd secretory phospholipase A2 receptor; DEC-205 receptor; 72 Kd and 92 Kd type IV ...
CS1 maint: Multiple names: authors list (link) Weissleder R, Nahrendorf M, Pittet MJ (2014). "Imaging macrophages with ... "SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions". Science. 352 (6282): 242-246. doi: ...
Squadrito ML, Etzrodt M, De Palma M, Pittet MJ (2013). "MicroRNA-mediated control of macrophages and its implications for ... Weissleder R, Nahrendorf M, Pittet MJ (2014). "Imaging macrophages with nanoparticles". Nat Mater. 13 (2): 125-38. doi:10.1038/ ... macrophages, monocytes and neutrophils. These cells are considered as drug targets in cancer immunotherapy. Pittet has ... "SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions". Science. 352 (6282): 242-246. doi: ...
Frequently, the term refers to circulating macrophages and has been used also for stationary macrophages fixed in tissues ( ... Macrophages arise from monocytes. Monocytes originate in the bone marrow upon which they are released into the blood stream. ... 112). In CT, they give rise to macrophages (histiocytes). Wandering Cells are probably amoeboid when alive but after fixations ... Fibrocytes, or fibroblasts and fat cells(adipocytes) are fixed cells, where as macrophages, monocytes, lymphocytes, plasma ...
... macrophage. Blood cell lineage Hematopoiesis Monocyte Macrophage Agranulocyte White blood cell. ... They mature into monocytes which, in turn, develop into macrophages. A typical monoblast is about 12 to 20 µm in diameter, has ... The monoblast is the first stage of monocyte-macrophage maturation. The developmental stages of the monoblast are: CFU-GM ( ...
Attracts macrophages, monocytes and neutrophils. Macrophage inflammatory proteins ENSG00000277632, ENSG00000274221 GRCh38: ... Chemokine (C-C motif) ligand 3 (CCL3) also known as macrophage inflammatory protein 1-alpha (MIP-1-alpha) is a protein that in ... Guan E, Wang J, Norcross MA (Apr 2001). "Identification of human macrophage inflammatory proteins 1alpha and 1beta as a native ... Menten P, Wuyts A, Van Damme J (Dec 2002). "Macrophage inflammatory protein-1". Cytokine & Growth Factor Reviews. 13 (6): 455- ...
Staining macrophages in Whipple's disease. It can be used to diagnose α1-antitrypsin deficiency if periportal liver hepatocytes ...
FPL3 is expressed by circulating monocytes, eosinophils, and basophils but not neutrophils; tissue macrophages and dendritic ...
Reticuloendothelial macrophages are most affected. Iron accumulates preferentially in Kupffer cells, which are located in the ... Reticuloendothelial macrophages, which can phagocytose red blood cells, are important in the iron recycling process. ... Intestinal iron absorption and release of iron from macrophages is increased. Thus, this form of the disease leads to elevated ... These individuals are likely to have liver and spleen iron overload, primarily in Kupffer cells and other macrophages. Because ...
Mycobacterium tuberculosis uses this ESX-1 secretion system to deliver virulence factors into host macrophage and monocyte ... such as macrophages and monocytes. If this C-terminus is cleaved off, the complex shows greatly reduced attachment ability. ...
Liu L, Zeng M, Stamler JS (1999). "Hemoglobin induction in mouse macrophages". Proceedings of the National Academy of Sciences ... Other cells that contain hemoglobin include the A9 dopaminergic neurons in the substantia nigra, macrophages, alveolar cells, ... they are removed from the circulation by the phagocytic activity of macrophages in the spleen or the liver or hemolyze within ... which is exclusively expressed on monocytes or macrophages. Within these cells the hemoglobin molecule is broken up, and the ...
Peptides are processed and presented by two classical pathways: In MHC class II, phagocytes such as macrophages and immature ... macrophages, B cells, and especially dendritic cells (DCs). An APC takes up an antigen, performs antigen processing, and ... "Mechanisms of phagocytosis in macrophages". Annu. Rev. Immunol. 17: 593-623. doi:10.1146/annurev.immunol.17.1.593. PMID ...
Those in dendritic cells have weaker bactericidal properties than those in macrophages and neutrophils. Also, macrophages are ... Macrophages and neutrophils are professional phagocytes in charge of most of the pathogen degradation, but they have different ... Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs). A phagosome is formed by the fusion of the ... Phagosome maturation in amoeba is very similar to that in macrophages, so they are used as a model organism to study the ...
HIV mainly targets lymphoid CD4+ T cells, but can infect other cells that express CD4 such as macrophages and dendritic cells ( ... Human IL-10 (hIL-10) suppresses the proliferation and cytokine production of all T cells and the activity of macrophages, but ... CD4+ T cells can also stimulate cells such as natural killer cells and macrophages via cytokines such as interferon-gamma, ... IFN-γ secreted by CD4 T cells can activate macrophages to phagocytose and digest intracellular bacteria and protozoa. In ...
2010). Lentiviruses and Macrophages: Molecular and Cellular Interactions. Caister Academic. ISBN 978-1-904455-60-8. .. ...
Lipopolysaccharide-activated murine macrophage model Antimalarial, larvicidal. S. mauritiana. Aerial parts. Methanol extract. ...
Macrophages rich in cholesterol are found in atherosclerotic tissue. Scavenger receptor CD36 is a class B scavenger receptor ... Moore, K. J.; Sheedy, F. J.; Fisher, E. A. (2013). "Macrophages in atherosclerosis: A dynamic balance". Nature Reviews ... Tocopherol decreases CD36 expression in human monocyte-derived macrophages". J Lipid Res. 42 (4): 521-527. PMID 11290823. CS1 ...
However, in J774 macrophages and phorbol ester-stimulated peritoneal macrophages, these treatments markedly reduced the ... In unstimulated peritoneal macrophages, which normally contain few tubular lysosomes and which exhibit relatively inefficient ... Tubular lysosomes accompany stimulated pinocytosis in macrophages.. J Swanson, E Burke, S C Silverstein ... A network of tubular lysosomes extends through the cytoplasm of J774.2 macrophages and phorbol ester-treated mouse peritoneal ...
They also modulate the expression of macrophage cell surface Ia antigens. One MAF is INTERFERON-GAMMA. Other factors ... Factors secreted by stimulated lymphocytes that prime macrophages to become nonspecifically cytotoxic to tumors. ... Macrophage-Activating Factors. Subscribe to New Research on Macrophage-Activating Factors Factors secreted by stimulated ... 01/01/1992 - "tularensis infection in mice induces the production of macrophage activating factors (MAFs) by spleen cells. ". ...
What is macrophage-activating factor? Meaning of macrophage-activating factor as a legal term. What does macrophage-activating ... Definition of macrophage-activating factor in the Legal Dictionary - by Free online English dictionary and encyclopedia. ... redirected from macrophage-activating factor). Also found in: Dictionary, Thesaurus, Medical, Financial, Encyclopedia. Factor. ... produces a potent macrophage-activating factor (Gc-MAF) (3).. Lectin immunoassay for macrophage-activating factor (Gc-MAF) ...
Macrophage colony-stimulating factor (M-CSF) is a lineage-specific, homodimeric growth factor that supports the proliferation ... Its etiology may in part be explained by proliferation and activation of monocyte/macrophage cells in bone marrow samples. ... Phase I study of continuous-infusion recombinant macrophage colony-stimulating factor in patients with metastatic melanoma ... In vitro studies have demonstrated antitumor activity of macrophage colony-stimulating factor-treated monocytes against ...
p,One of the first cytokines described, MIF (macrophage migration inhibitory factor) was originally identified in studies of ... delayed hypersensitivity reactions where it was shown to inhibit macrophage migration. It is an important mediator of the ... "Macrophage migration inhibitory factor reduces the growth of virulent Mycobacterium tuberculosis in human macrophages."Infect. ... "A macrophage migration inhibitory factor is expressed in the differentiating cells of the eye lens."Proc. Natl. Acad. Sci. U.S. ...
Purchase Recombinant Human Granulocyte-macrophage colony-stimulating factor(CSF2). It is produced in E.coli. High purity. Good ... Recombinant Human Granulocyte-macrophage colony-stimulating factor(CSF2). Recombinant Human Granulocyte-macrophage colony- ... Recombinant Human Granulocyte-macrophage colony-stimulating factor(CSF2) ( Yeast-CSB-YP006045HU ). *Recombinant Human ... Recombinant Human Granulocyte-macrophage colony-stimulating factor protein(CSF2) (Active) ( E.coli-CSB-AP002081HU ) ...
Macrophage migration inhibitory factor (MIF) activates macrophages, promotes delayed-type hypersensitivity reaction, and ... Serum and BAL macrophage migration inhibitory factor levels in HIV infected Tanzanians with pulmonary tuberculosis or other ...
define Macrophage Migration-Inhibitory Factors. Explain Macrophage Migration-Inhibitory Factors. What is Macrophage Migration- ... Macrophage Migration-Inhibitory Factors. Medical Dictionary -> Macrophage Migration-Inhibitory Factors. Search: Macrophage ... Proteins released by sensitized lymphocytes and possibly other cells that inhibit the migration of macrophages away from the ... Inhibitory Factors? Macrophage Migration-Inhibitory Factors FAQ. ...
4A) ⇓ . DTH site biopsies also disclosed ingress of macrophages (Fig. 4B) ⇓ and of natural killer cells (Fig. 4C) ⇓ . Extensive ... 2C) ⇓ . Macrophages were also detected (Fig. 2D) ⇓ . Neutrophils and eosinophils, usually present near vaccine cells in the ... 2E) ⇓ . CD3+ T-cells also appeared near DCs and macrophages recruited to vaccine sites. Frequent CD8+ T-cells were consistently ... Notably, DCs and macrophages were recruited for antigen processing by paracrine GM-CSF secretion at tumor vaccination sites ( ...
induced macrophages by dual stimulation with IFN-γ and IL-4, which are the inducers for M1 and M2 phenotype macrophages, ... 5. Macrophage Functional Diversity in Atherosclerosis. 5.1. M1 and M2 Macrophages. As with the well-established T cell ... Other Macrophage Phenotypes. Along with a deep understanding of the phenotypes and functions of lesional macrophages, it has ... 4. Macrophages in Advanced Atherosclerosis. 4.1. Macrophages and Fibrous Caps. Stable plaques with intact fibrous caps rarely ...
Tissue biology perspective on macrophages.. Okabe Y1, Medzhitov R1.. Author information. 1. Howard Hughes Medical Institute, ... Macrophages are essential components of mammalian tissues. Although historically known mainly for their function in host ... In addition, tissue-resident macrophages have many tissue-specific functional characteristics, which are a reflection of ... Here we discuss the emerging views of macrophage biology from evolutionary, developmental and homeostatic perspectives. ...
... techniques to study macrophages and covers numerous topics such as in vitro culture models for murine and human macrophages. ... functional analyses of macrophages; and transgenic models of macrophage depletion and macrophage targeting. Written in the ... Macrophages. Book Subtitle. Methods and Protocols Editors. * Germain Rousselet Series Title. Methods in Molecular Biology. ... The chapters A Simple Multi-Step Protocol for Differentiating Human Induced Pluripotent Stem Cells into Functional Macrophages ...
... Joan S. Hunt,1,2 Lance Miller,2 and Jeralyn Sue Platt1 ... Joan S. Hunt, Lance Miller, and Jeralyn Sue Platt, "Hormonal Regulation of Uterine Macrophages," Developmental Immunology, vol ...
This procedure usually gets you ,95% pure macrophages by non-specific esterase staining. If you want inflammatory macrophages, ... Isolation of Macrophages. Jay Mone jmone at MARAUDER.MILLERSV.EDU Tue Jun 2 06:47:20 EST 1998 *Previous message: Isolation of ... Dave: To isolate resident peritoneal macrophages, kill the mouse, and immediately inject the peritoneum with about 5 mls of pre ...
Louis have found that as immune cells called macrophages age, the changes in those older cells can increase the risks for age- ... Louis have found that as immune cells called macrophages age, the changes in those older cells can increase the risks for age- ...
... alveolar macrophages. To test whether the spleen participates in macrophage responses during tumor progression, we ... Origins of tumor-associated macrophages and neutrophils. Virna Cortez-Retamozo, Martin Etzrodt, Andita Newton, Philipp J. Rauch ... Origins of tumor-associated macrophages and neutrophils. Virna Cortez-Retamozo, Martin Etzrodt, Andita Newton, Philipp J. Rauch ... Tumor-associated macrophages (TAMs) can stimulate tumor growth (1⇓⇓-4), and their density is associated with adverse outcomes ...
Macrophage News and Research. RSS A macrophage is a type of white blood cell that surrounds and kills microorganisms, removes ... Macrophage to Foam Cell Differentiation Pathway. *What is the difference Between a Phagocyte, Macrophage, Neutrophil and ... UAB researchers awarded $2.3 million grant to study macrophage circadian rhythms in heart failure Researchers at the University ... Glioblastomas, the deadliest type of brain tumor in adults, attract "turncoats." These are macrophages, a type of immune cell, ...
... brett at BORCIM.WUSTL.EDU brett at BORCIM.WUSTL.EDU Mon Apr 18 12:29:40 EST 1994 *Previous ... recently frank chisari from the scripps used carageenan to bump off the macrophages in vivo. i dont have the ref handy, but it ...
Create healthcare diagrams like this example called Macrophage in minutes with SmartDraw. SmartDraw includes 1000s of ... Macrophage. Create healthcare diagrams like this example called Macrophage in minutes with SmartDraw. SmartDraw includes 1000s ... Macrophage. Graphic of macrophage grabbing foreign body in blood stream.. LifeART Collection Images Copyright © 1989-2001 by ...
... leading to a reduced rate of reproduction among bacteria in macrophages. ... When macrophages are deprived of oxygen. University of Erlangen-Nuremberg. Journal. Cell Reports. Keywords. *IMMUNOLOGY/ ... Macrophages are a type of phagocyte and belong to the congenital immune system, where they have a key role to play in defending ... When macrophages are deprived of oxygen How pathogens are controlled when tissue is deprived of adequate oxygen supply ...
Macrophages are the major producers of TNFα and interestingly are also highly responsive to TNFα. Aberrant TNFα production and ... In this review we discuss the discovery of TNFα and its actions especially in regulating macrophage biology. Given its ... Tumor necrosis factor-α signaling in macrophages.. Parameswaran N1, Patial S. ...
The result was benign appearing follicular cells and macrophages. I have pain in my neck in the area of the thyroid. Difficulty ... follicular cells and macrophages mbooher1 I just had a needle biopsy of two nodules on each side of my thyroid. The result was ... follicular cells and macrophages. I just had a needle biopsy of two nodules on each side of my thyroid. The result was benign ... appearing follicular cells and macrophages. I have pain in my neck in the area of the thyroid. Difficulty swallowing and my ...
Macrophage dynamics in diabetic wound dealing. Waugh HV, Sherratt JA. Bull Math Biol 2006 Jan;68(1):197-207 16794927 , Abstract ... As a consequence of this, we put forward a suggestion for treatment based on rectifying the macrophage phenotype imbalance. ... As a consequence of this, we put forward a suggestion for treatment based on rectifying the macrophage phenotype imbalance. ... SBML L2V4 representation of Waugh2006 - Diabetic Wound Healing - Macrophage Dynamics. 49.81 KB. Preview , Download. ...
Macrophage definition, a large white blood cell, occurring principally in connective tissue and in the bloodstream, that ... macrophage. in Science. macrophage. [măk′rə-fāj′]. *Any of various large white blood cells that play an essential immunologic ... macrophage. in Medicine. macrophage. [măk′rə-fāj′]. n.. *Any of the large phagocytic cells found in the reticuloendothelial ... macrophage. macrophage. noun. *any large phagocytic cell occurring in the blood, lymph, and connective tissue of vertebratesSee ...
Macrophages are large, specialized cells that recognize, engulf and destroy target cells. The term macrophage is formed by the ... Macrophages are important cells of the immune system that are formed in response to an infection or accumulating damaged or ... Macrophages are large, specialized cells that recognize, engulf and destroy target cells. The term macrophage is formed by the ... Macrophages may have different names according to where they function in the body. For example, macrophages present in the ...
  • Cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes. (cusabio.com)
  • In humans, deglycosylation of Gc-globulin, involving stepwise removal of [beta]-galactose and sialic acid from the trisaccharide, leaving N-acetyl-galactosamine (GalNAc), produces a potent macrophage-activating factor (Gc-MAF) (3). (thefreedictionary.com)
  • Macrophages are essential components of mammalian tissues. (nih.gov)
  • Here, we show that the incorporation of macrophages into muscle tissues engineered from adult-rat myogenic cells enables near-complete structural and functional repair after cardiotoxic injury in vitro. (nature.com)
  • We then show that rat bone-marrow-derived macrophages or human blood-derived macrophages resident within the in vitro engineered tissues stimulate muscle satellite cell-mediated myogenesis while significantly limiting myofibre apoptosis and degeneration. (nature.com)
  • Moreover, bone-marrow-derived macrophages within engineered tissues implanted in a mouse dorsal window-chamber model augmented blood vessel ingrowth, cell survival, muscle regeneration and contractile function. (nature.com)
  • Recently, there has been considerable progress in our understanding of human macrophage biology in different tissues, including the intestines. (jimmunol.org)
  • 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. (jci.org)
  • 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. (ucl.ac.uk)
  • However the range of genes upregulated and functions carried out by macrophages in such hypoxic tissues are not fully understood. (coventry.ac.uk)
  • Macrophages are extremely versatile cells, distributed throughout all tissues, involved in numerous functions, and equipped with many sensing receptors and effector molecules. (els.net)
  • These diverse stress signals lead to further reprogramming of macrophages with different effect sizes and kinetics in macrophages derived from different tissues. (els.net)
  • Similar to stem cells differentiating to make your body's tissues, the immune system's macrophages pick a life path, differentiating into macrophages that recruit resources for wound repair or macrophages that recruit resources for wound sterilization. (fightaging.org)
  • Macrophages are cells of the body's immune system that are found in the tissues rather than in the circulating blood. (sciencephoto.com)
  • 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. (medindia.net)
  • Sivanjah's photo visualising macrophages in the adult mouse testis has been selected to be displayed at the inaugural Day of Immunology photography exhibition. (uni-giessen.de)
  • 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. (els.net)
  • 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. (eurekalert.org)
  • 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. (news-medical.net)
  • 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. (nih.gov)
  • 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. (medscape.com)
  • Macrophage activation syndrome is characterized by a highly stimulated but ineffective immune response. (medscape.com)
  • Recent studies have shown that MUNC 13-4 polymorphisms are associated with macrophage activation syndrome in some patients with SJIA. (medscape.com)
  • These findings were supported by a recent study of hepatic biopsy samples in patients with various types of HLH, including macrophage activation syndrome. (medscape.com)
  • 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. (medscape.com)
  • Moreover, very high levels of IL-18 have been reported in 2 patients with SJIA and macrophage activation syndrome. (medscape.com)
  • [ 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. (medscape.com)
  • Macrophages can be classified on basis of the fundamental function and activation. (wikipedia.org)
  • Macrophage responses to PPAR and LXR activation. (els.net)
  • Although Notch signaling participates in various aspects of immunity, its role in macrophage activation remains undetermined. (ahajournals.org)
  • Activation of the hypothalamic-pituitary-adrenal axis leads to production of glucocorticoids that cause decreased production of IL-12 by macrophages. (wikipedia.org)
  • Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages. (sigmaaldrich.com)
  • Therefore, it is of utmost importance to understand how macrophage activation is regulated and orchestrated. (els.net)
  • In fact, previous experimental approaches favoured such dichotomous models of macrophage activation. (els.net)
  • 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. (els.net)
  • To describe such plasticity, and based on computational modelling of transcriptome data, we have introduced the multidimensional model of macrophage activation. (els.net)
  • The multidimensional model of macrophage activation describes the input‐specific cellular programming of macrophages in response to stimulation. (els.net)
  • Multidimensional model of macrophage activation. (els.net)
  • 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. (els.net)
  • Ginhoux F, Schultze JL, Murray PJ, Ochando J and Biswas SK (2015) New insights into the multidimensional concept of macrophage ontogeny, activation and function. (els.net)
  • Murine macrophage cell line RAW264.7 stably expressing MKP-2 was used to study the regulation of MKP-2 in macrophages in response to saturated free fatty acid (FFA) and its role in macrophage M1/M2 activation. (doaj.org)
  • c-Jun N-terminal kinase (JNK)- and p38-specific inhibitors were used to examine the mechanisms by which MKP-2 regulates macrophage activation and macrophage-adipocytes interaction.HFD changed the expression of MKP-2 in WAT, and MKP-2 was highly expressed in the stromal vascular cells (SVCs). (doaj.org)
  • MKP-2 inhibited macrophage M1 activation through JNK and p38. (doaj.org)
  • Inhibition of TNFα expression in macrophages by SSZ is due to the induction of apoptosis and involves the activation of caspase 8. (tudelft.nl)
  • 1-1 1-3 1-5 While the precise mechanisms employed by the macrophages to modulate T cells are incompletely understood, it is clear that their overall efficiency in this regard is a reflection of their maturation/activation status. (bmj.com)
  • and transgenic models of macrophage depletion and macrophage targeting. (springer.com)
  • 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. (biologists.org)
  • 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. (sciencemag.org)
  • A majority of macrophages are stationed at strategic points where microbial invasion or accumulation of foreign particles is likely to occur. (wikipedia.org)
  • 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. (els.net)
  • 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. (els.net)
  • 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. (jci.org)
  • 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. (coventry.ac.uk)
  • Answering this question is of special interest in globoid cell leukodystrophy (GLD), a genetic fatal demyelinating disease, because its rapidly progressive demyelination in the nervous system is accompanied by a characteristic accumulation of numerous globoid macrophages. (jneurosci.org)
  • discuss the pathogenesis and co-mortality displayed by two macrophage-inhabiting microbes (HIV and Mycobacterium Tuberculosis) and their influence on macrophage polarization. (frontiersin.org)
  • In adipose tissue, distinction between M1 and M2 macrophage polarization can be monitored by assessing the expression of selected markers. (wikipedia.org)
  • Adiopose tissue macrophage polarization was summarized in a recent review article Appari M et al. (wikipedia.org)
  • Macrophage polarization was assessed by double staining with pSTAT1 or CMAF followed by CD68 or CD163. (lww.com)
  • 1-5 Macrophages adapt to the local microenvironment and acquire various functions associated with physiological and pathological processes. (ahajournals.org)
  • This model showcases the capability of macrophages of integrating signals they derive from their microenvironment to signal input‐specific functional programmes. (els.net)
  • Macrophages integrate signals from their microenvironment, which results in signal input‐specific functional outcomes. (els.net)
  • 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. (nsti.org)
  • Having found erythropoietin effects on dendritic cells thus led to the question of whether macrophages act as target cells to erythropoietin. (haematologica.org)
  • Lastly, we describe the therapeutic potential of cardiac macrophages in the context of cell-mediated cardio-protection. (mdpi.com)
  • These data represent a preferential apoptotic signaling pathway of macrophages as specific target points for the prevention and therapeutic modulation of periprosthetic osteolysis. (ingentaconnect.com)
  • 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. (coventry.ac.uk)
  • 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. (ahajournals.org)
  • Monocyte-derived macrophages and several macrophage-like cell lines were exposed to SSZ in vitro, and the effect on TNFα expression was monitored by reverse transcriptase-polymerase chain reaction and Western blot analysis. (tudelft.nl)
  • Design and Methods EPO effects on macrophages were investigated both in-vivo and in-vitro. (haematologica.org)
  • The in-vitro effects of erythropoietin on macrophage surface markers and function were investigated in murine bone marrow-derived macrophages treated with recombinant human erythropoietin. (haematologica.org)
  • Results Erythropoietin effects on macrophages were found under both the in-vivo and in-vitro experiments. (haematologica.org)
  • But as little as 20 minutes later, the drug had been taken up by macrophages within the tumors. (genengnews.com)
  • 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. (mdanderson.org)
  • 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. (aacrjournals.org)
  • 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. (sciencemag.org)
  • In murine atherosclerotic lesions, we found that macrophages turn over rapidly, after 4 weeks. (nature.com)
  • In this issue of the JCI, Guo, Akahori, and colleagues show that CD163+ macrophages promote angiogenesis, vessel permeability, and leucocyte infiltration in human and mouse atherosclerotic lesions through a mechanism involving hemoglobin:haptoglobin/CD163/HIF1α-mediated VEGF induction. (jci.org)
  • AT1 receptor antagonists may be useful to suppress oxidative stress of macrophages in atherosclerotic lesions. (ahajournals.org)
  • 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. (eurekalert.org)
  • Macrophages are important cells of the immune system that are formed in response to an infection or accumulating damaged or dead cells. (news-medical.net)
  • In this way, macrophages provide a first line of defence in protecting the host from infection. (news-medical.net)
  • 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. (medindia.net)
  • 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. (medindia.net)
  • 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. (mdpi.com)
  • 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. (ucl.ac.uk)
  • The researchers say that macrophages can be an important reservoir of HIV infection that lingers away from the reach of existing treatments. (ucl.ac.uk)
  • 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. (ucl.ac.uk)
  • 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. (nih.gov)
  • 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. (nih.gov)
  • 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. (nih.gov)
  • The interaction of macrophages and T cells plays an important role in the immune response during TB infection. (aimsciences.org)
  • To better understand the dynamics of TB infection and Treg cell regulation, we build a mathematical model using a system of differential equations that qualitatively and quantitatively characterizes the dynamics of macrophages, Th1 and Treg cells during TB infection. (aimsciences.org)
  • Tissue biology perspective on macrophages. (nih.gov)
  • Here we discuss the emerging views of macrophage biology from evolutionary, developmental and homeostatic perspectives. (nih.gov)
  • In this review we discuss the discovery of TNFα and its actions especially in regulating macrophage biology. (nih.gov)
  • This volume looks at--and discusses the techniques of--a range of areas in biology in which macrophage migration inhibitory factor (MIF) is studied. (springer.com)
  • 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. (springer.com)
  • 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. (coventry.ac.uk)
  • A macrophage is a type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. (news-medical.net)
  • The immune system involving the actions of macrophages is amazingly complex and harmoniously coordinated, recognizing and removing invading particles and coordinating with the T-cells to provide the necessary protection of the body. (newworldencyclopedia.org)
  • 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. (newworldencyclopedia.org)
  • Macrophages are a type of leukocyte or white blood cell, which include several types of blood cells that have a nucleus and cytoplasm and are part of the immune system . (newworldencyclopedia.org)
  • When the immune system is unable to eliminate substances perceived as foreign, it produces a granuloma, composed mostly of macrophages, attempting to wall off the non‐self material. (els.net)
  • 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. (ucl.ac.uk)
  • However, researchers can now successfully flip M2 macrophages into their wound-sterilizing cousins, called "M1" or "kill-type" macrophages, which, contrary to promoting the growth of new tissue, may aid the immune system in clearing the body of cancer. (fightaging.org)
  • The intricate balance between phenotypically heterogeneous populations of macrophages in the heart have profound and highly orchestrated effects during different phases of myocardial infarction. (mdpi.com)
  • Our job now is to get a better understanding of what these different macrophage populations are doing. (medindia.net)
  • Macrophages are one of the most versatile cell populations within multicellular organisms. (els.net)
  • Splenic granulocyte and macrophage progenitors and their descendants were likewise identified in clinical specimens. (pnas.org)
  • As the serum concentration of iron decreases, iron accumulates in hepatic and splenic macrophages. (sciencemag.org)
  • 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. (abcam.com)
  • In-vivo treatment led to increased numbers of splenic macrophages, and of the splenic macrophages expressing CD11b, CD80 and major histocompatibility complex class II. (haematologica.org)
  • Splenic macrophages isolated from DP rats at 33,100,120, and 140 days of age showed no enhanced islet killing compared with diabetes-resistant rats. (diabetesjournals.org)
  • These macrophages can self-replicate and likely regulate the normal function of our arteries. (medindia.net)
  • Macrophages are large, specialized cells that recognize, engulf and destroy target cells. (news-medical.net)
  • 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. (newworldencyclopedia.org)
  • 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. (sciencemag.org)
  • Macrophages are critical for controlling many bacterial infections but many pathogens, including Mycobacterium tuberculosis , can hijack these cells and use them as sites of replication. (rockefeller.edu)
  • We have utilized cutting-edge mass spectrometry techniques to comprehensively probe the interactions between macrophages and three intracellular bacterial pathogens, M. tuberculosis , Salmonella, and Listeria . (rockefeller.edu)
  • Breast milk AKGs are metabolized by adipose tissue macrophages (ATMs) to platelet-activating factor (PAF), which ultimately activates IL-6/STAT3 signaling in adipocytes and triggers BeAT development in the infant. (jci.org)
  • Increased number of adipose tissue macrophages correlates with increased adipose tissue production of proinflammatory molecules and might therefore contribute to the pathophysiological consequences of obesity (e.g. insulin resistance, type 2 diabetes). (wikipedia.org)
  • Thus, they are markedly distinct from monocyte-derived macrophages invading after local disturbance of nerve integrity. (jimmunol.org)
  • This inhibition prevents the expression of a subset of target genes of the transcription factor nuclear factor κB (NF-κB), which functions in macrophage survival. (sciencemag.org)
  • In addition, ADDA blocked LPS-mediated macrophage migration and this was associated with inhibition of LPS-induced Src and FAK phosphorylation as well as Src expression in a concentration dependent manner. (thefreedictionary.com)
  • The authors indicate that this inhibition of critical cellular functions in cultured alveolar macrophages suggests that inhalation of airborne silage or grain dust particulates contaminated with patulin could have harmful effects on normal macrophage functions in workers. (cdc.gov)
  • We first found that only PTEN-deficiency, but not other common genetic alterations, is associated with macrophage infiltration in glioblastoma," Chen said. (mdanderson.org)
  • These findings, as well as those reported previously, suggest that the melanoma cell provides the RNA, protein, and precursors which initiate macrophage DNA synthesis. (rupress.org)
  • Recently, specific macrophages dedicated to homeostatic peripheral nerves have come into focus. (jimmunol.org)
  • 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. (thefreedictionary.com)
  • Gordon S and Martinez‐Pomares L (2017) Physiological roles of macrophages. (els.net)
  • And unlike wound-healing macrophages, Mregs do not induct arginase, so they do not contribute to the production of the extracellular matrix. (wikipedia.org)
  • To study the role of mast cell and macrophage counts in the planning of treatment and predicting the treatment outcome. (thefreedictionary.com)
  • Next, the researchers will study how these resident macrophages interact with their tissue environment and exactly what role they might play in cardiovascular disease. (medindia.net)
  • however, the role of these macrophages in atherogenesis has been unclear. (jci.org)
  • 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. (rupress.org)
  • Airway macrophages (AMs) are important cell types in the lung, playing a pivotal role in host defense. (sciencemag.org)
  • These experiments suggested that melanoma proteins played an important role in the initiation of macrophage DNA synthesis. (rupress.org)
  • 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. (medicalxpress.com)
  • 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. (coventry.ac.uk)
  • 15 16 These investigations suggest not only that Ang II produced by macrophages affects neighboring cells such as smooth muscle cells and fibroblasts but also that Ang II plays a role in macrophages per se through the autocrine/paracrine system. (ahajournals.org)