Regulation of major histocompatibility gene expression in human vascular smooth muscle cells.
Regulation of major histocompatibility gene expression in human vascular smooth muscle cells.
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人血管平滑肌细胞主要组织相容性基因表达的调节。
DOI：
10.1161/01.atv.9.3.279
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Libby,P
中科院分区：
文献类型：
--
作者：
Warner,SJ;Friedman,GB;Libby,P
人类动脉粥样瘤(但不是正常血管)含有大量的平滑肌细胞(SMC)，这些细胞携带II类主要组织相容性(MHC)抗原。这些病变还含有能够分泌细胞因子的白细胞，这些细胞因子可能调节SMC的功能。由于血管病变中存在免疫激活的(II+)SMC的形态学证据，我们研究了细胞因子对培养的人血管SMC MHC基因表达的调节。在基础培养条件下，经Northern印迹法检测到MHC表达I类MHC，用单抗W6/32进行酶联免疫分析，检测到MHC产物表达。未刺激的SMC很少或根本不含II类MHC基因(用人类白细胞抗原DRα基因检测)或表面抗原(用单抗I2检测)。3天后，活化的人白细胞分泌产物(混合白细胞反应的无细胞上清液)诱导SMC表达II类MHC抗原。干扰素(干扰素)-α或-β(1000U/ml作用72小时)可增加SMC中I类MHC的mRNA含量和表面抗原，但不改变II类的表达。免疫干扰素是一种能诱导经典抗原提呈细胞、上皮细胞和内皮细胞表达I型MHC的白细胞产物，它不仅能增加SMC对I型MHC的表达，而且还能诱导大量的II型MHC基因和表面抗原的表达。干扰素-γ(ED50约为10U/ml)在2~3天后最大限度地增加II类MHC mRNA的表达，在1~4天内呈线性增加。免疫组织化学结果显示，在基础培养条件下，培养的人SMC中仅有少量的II类+SMC，但在干扰素-γ作用3d后，均一地表达高水平的DR抗原。白介素1(IL-1α或β)、肿瘤坏死因子α(TNF)和内毒素都不能改变SMC的II类分子的表达。活化的白细胞局部分泌干扰素-γ可能是人类动脉粥样硬化中存在HLA-DR+SMC的原因之一。SMC的免疫激活可能参与了血管炎和动脉硬化的发病，特别是在移植心脏的冠状动脉中发现的形式。
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.