Biomaterial Database

Regulation of major histocompatibility gene expression in human vascular smooth muscle cells. 1989

S J Warner, and G B Friedman, and P Libby

Department of Medicine (Cardiology), Tufts University, Boston, MA 02111.

Human atheromata, but not normal blood vessels, contain numerous smooth muscle cells (SMC) that bear class II major histocompatibility (MHC) antigens. These lesions also contain leukocytes that can secrete cytokines, which may modulate SMC functions. Because of morphologic evidence for immune-activated (class II+) SMC in vascular lesions, we studied the regulation by cytokines of MHC gene expression in SMC cultured from human vessels. Under basal conditions, these SMC contained mRNA for class I MHC (detected by Northern blotting with a cDNA probe for HLA-B7) and expressed surface class I MHC product determined by enzyme-linked immunoassay with monoclonal antibody (MAb) W6/32. Unstimulated SMC contained little or no class II MHC mRNA (probed with HLA-DR alpha cDNA) or surface antigen (examined using MAb I2). Secretory products of activated human leukocytes (the cell-free supernatant of a mixed leukocyte reaction) induced class II MHC antigen expression by SMC after 3 days. Treatment of SMC with interferon (IFN)-alpha or -beta (1000 U/ml for 72 hours) increased class I MHC mRNA content and surface antigen but did not alter class II expression. Immune IFN (IFN-gamma), a leukocyte product known to induce class II MHC expression in classical antigen presenting cells as well as epithelial and endothelial cells, not only increased class I MHC expression by SMC but also induced substantial levels of class II MHC mRNA and surface antigen. IFN-gamma (ED50 approximately 10 U/ml) increased class II MHC mRNA maximally after 2 to 3 days and surface expression linearly from 1 to 4 days. Immunohistochemical study demonstrated few class II+ SMC in cultured human SMC under basal conditions but homogeneous expression of high levels of DR antigen after exposure to IFN-gamma for 3 days. Neither interleukin-1 (IL-1 alpha or beta), tumor necrosis factor alpha (TNF), nor endotoxin altered class II expression by SMC. Local secretion of IFN-gamma by activated leukocytes may account for the presence of HLA-DR+ SMC in the human atheroma. Immune activation of SMC might participate in the pathogenesis of vasculitis and arteriosclerosis, particularly in the form found in the coronary arteries of transplanted hearts.

UI	MeSH Term	Description	Entries
D007372	Interferons	Proteins secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions.	Interferon
D007959	Lymphocyte Culture Test, Mixed	Measure of histocompatibility at the HL-A locus. Peripheral blood lymphocytes from two individuals are mixed together in tissue culture for several days. Lymphocytes from incompatible individuals will stimulate each other to proliferate significantly (measured by tritiated thymidine uptake) whereas those from compatible individuals will not. In the one-way MLC test, the lymphocytes from one of the individuals are inactivated (usually by treatment with MITOMYCIN or radiation) thereby allowing only the untreated remaining population of cells to proliferate in response to foreign histocompatibility antigens.	Leukocyte Culture Test, Mixed,Mixed Lymphocyte Culture Test,Mixed Lymphocyte Reaction,Mixed Leukocyte Culture Test,Mixed Leukocyte Reaction,Leukocyte Reaction, Mixed,Leukocyte Reactions, Mixed,Lymphocyte Reaction, Mixed,Lymphocyte Reactions, Mixed,Mixed Leukocyte Reactions,Mixed Lymphocyte Reactions
D008285	Major Histocompatibility Complex	The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.	Histocompatibility Complex,Complex, Histocompatibility,Complex, Major Histocompatibility,Complices, Histocompatibility,Complices, Major Histocompatibility,Histocompatibility Complex, Major,Histocompatibility Complices,Histocompatibility Complices, Major,Major Histocompatibility Complices
D009131	Muscle, Smooth, Vascular	The nonstriated involuntary muscle tissue of blood vessels.	Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D002478	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.	Cultured Cells,Cell, Cultured,Cultured Cell
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000949	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.	Antigens, Immune Response,Class II Antigens,Class II Histocompatibility Antigen,Class II Major Histocompatibility Antigen,Ia Antigens,Ia-Like Antigen,Ia-Like Antigens,Immune Response Antigens,Immune-Associated Antigens,Immune-Response-Associated Antigens,MHC Class II Molecule,MHC II Peptide,Class II Antigen,Class II Histocompatibility Antigens,Class II MHC Proteins,Class II Major Histocompatibility Antigens,Class II Major Histocompatibility Molecules,I-A Antigen,I-A-Antigen,IA Antigen,MHC Class II Molecules,MHC II Peptides,MHC-II Molecules,Antigen, Class II,Antigen, I-A,Antigen, IA,Antigen, Ia-Like,Antigens, Class II,Antigens, Ia,Antigens, Ia-Like,Antigens, Immune-Associated,Antigens, Immune-Response-Associated,I A Antigen,II Peptide, MHC,Ia Like Antigen,Ia Like Antigens,Immune Associated Antigens,Immune Response Associated Antigens,MHC II Molecules,Molecules, MHC-II,Peptide, MHC II,Peptides, MHC II
D000954	Antigens, Surface	Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.	Cell Surface Antigens,Surface Antigens,Surface Markers, Immunological,Cell Surface Antigen,Immunologic Surface Markers,Markers, Immunological Surface,Surface Antigen,Surface Markers, Immunologic,Antigen, Cell Surface,Antigen, Surface,Antigens, Cell Surface,Immunological Surface Markers,Markers, Immunologic Surface,Surface Antigen, Cell,Surface Antigens, Cell
D001685	Biological Factors	Endogenously synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS.	Biologic Factors,Biological Factor,Factor, Biologic,Factor, Biological,Factors, Biological,Biologic Factor,Factors, Biologic
D015395	Histocompatibility Antigens Class I	Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.	Class I Antigen,Class I Antigens,Class I Histocompatibility Antigen,Class I MHC Protein,Class I Major Histocompatibility Antigen,MHC Class I Molecule,MHC-I Peptide,Class I Histocompatibility Antigens,Class I Human Antigens,Class I MHC Proteins,Class I Major Histocompatibility Antigens,Class I Major Histocompatibility Molecules,Human Class I Antigens,MHC Class I Molecules,MHC-I Molecules,MHC-I Peptides,Antigen, Class I,Antigens, Class I,I Antigen, Class,MHC I Molecules,MHC I Peptide,MHC I Peptides,Molecules, MHC-I,Peptide, MHC-I,Peptides, MHC-I