Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The patterns of induced major histocompatibility antigen expression on indigenous cellular elements of heterotopic rat cardiac grafts were determined by immunohistologic methods in a variety of donor-recipient combinations. Heart grafts were studied in combined full-MHC- and non-MHC-disparate combinations, isolated intra-MHC-disparate combinations, and non-MHC-disparate combinations. The pattern of class II expression on cellular constituents of the grafts was highly variable and critically dependent upon the nature of the specific unidirectional donor-recipient combination. No uniform pattern of class II expression emerged that was clearly predictive of rapidity of rejection or of protracted survival. However, vasculitis was confined to grafts in combinations in which induced class II expression on graft large vessel endothelium was present. Sites of vasculitis were never encountered in the absence of induced class II expression on overlying endothelium. Vasculitis and associated induced class II expression on large vessel endothelium were present in rapidly rejecting grafts and in grafts with indefinite survival. In the latter, vasculitis was shown to progress to a late phase of occlusive intimal thickening. Induced class I expression on graft cardiac myofibers was present in all the genetically disparate donor-recipient combinations examined in this study, irrespective of the length of graft survival. This investigation has shown that no uniform stereotyped pattern of MHC antigen expression on cellular constituents correlates with the length of graft survival. However, induced class II expression on graft large vessel endothelium is closely associated with vasculitis, which can directly progress to occlusive intimal thickening in grafts with prolonged survival.
 ...
PMID:Multiple patterns of MHC class II antigen expression on cellular constituents of rat heart grafts. Lack of correlation with graft survival, but strong correlation with vasculitis. 203 Dec 76

Arterial smooth muscle cells (SMC) express major histocompatibility complex (MHC) class II antigens in experimental vasculitis and in the human atherosclerotic plaque. We have therefore studied the regulation of expression of MHC antigens in cultured human arterial SMC, using immunofluorescence, radioimmunoprecipitation and a quantitative cell-surface immunoradiometric assay. SMC expressed class I, but not class II, antigens on their cell surfaces under basal conditions. Treatment of SMC with recombinant or natural interferon-gamma (IFN-gamma) induced expression of class II antigens in the following order of intensity, DR greater than DP greater than DQ. HLA-DR protein in SMC showed the same MW as that synthesized by B-lymphoblastoid cells. Antibodies to IFN-gamma blocked all HLA-DR-inducing activity in mixed leucocyte reaction (MLR) supernatants and PHA-stimulated peripheral blood mononuclear cell (PBMC)-conditioned media, indicating that IFN-gamma is the only lymphokine secreted under these conditions that is capable of de novo induction of HLA-DR expression in SMC. Treatment of SMC with recombinant human tumour necrosis factor-alpha (TNF) or lymphotoxin (LT) did not per se induce class II antigen expression. However, both TNF and LT substantially enhanced IFN-gamma-induced expression of HLA-DQ while decreasing that of HLA-DP. TNF, but not LT, increased HLA-DR expression. Also, in dermal fibroblasts, IFN-gamma-induced HLA-DP expression was significantly inhibited in the presence of TNF. These data demonstrate that TNF and LT differentially modulate IFN-gamma-induced MHC antigen expression in mesenchymal cells. The fact that SMC can express MHC class II antigens suggests that this cell type may serve as an accessory cell in the initiation of the immune response.
 ...
PMID:MHC class II antigen expression in human vascular smooth muscle cells is induced by interferon-gamma and modulated by tumour necrosis factor and lymphotoxin. 210 84

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.
 ...
PMID:Regulation of major histocompatibility gene expression in human vascular smooth muscle cells. 247 Mar 42

Takayasu's arteritis (TA) is a chronic large vessel vasculitis. The physiopathology of TA has not been completely elucidated, but it appears to be multifactorial and to mainly involve cellular immunity. The pathologic sequence could implicate stimulation from an antigen that triggers heat shock protein (HSP)-65 expression in aortic tissue which, in turn, induces MHC class I-related chain A (MICA). T-cells and natural killer (NK) cells expressing NKG2D receptors could recognize MICA, resulting in acute inflammation. Pro-inflammatory cytokines released from these infiltrating cells induce matrix metalloproteinases and amplify the inflammatory response, inducing more MHC antigen and costimulatory molecule expression on vascular cells and, thus, recruiting more mononuclear cells. Alpha-beta T-cells then infiltrate and specifically recognize one or a few autoantigens presented by a shared epitope associated with specific MHC on the dendritic cells (DC). These DC simultaneously cooperate to some extent with B-cells and determine a humoral immunity mainly constituted by anti-endothelial cell autoantibodies that could trigger complement-dependent cytotoxicity against endothelial cells. The use of corticosteroids and of other immunosuppressive agents can bring TA into remission in most patients. A better understanding of the immunological mechanisms responsible for the vascular injury has led to trials of anti-TNF-alpha agents with encouraging results. In the near future, new drugs specifically designed to target some of the mechanisms described above may be able to expand the physician's therapeutic arsenal in TA.
 ...
PMID:Takayasu's arteritis: An update on physiopathology. 1676 72