ADHESION MOLECULES ON MURINE BRAIN MICROVASCULAR ENDOTHELIAL-CELLS - EXPRESSION AND REGULATION OF ICAM-1 AND LGP-55

ADHESION MOLECULES ON MURINE BRAIN MICROVASCULAR ENDOTHELIAL-CELLS - EXPRESSION AND REGULATION OF ICAM-1 AND LGP-55
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DOI:
10.1016/0165-5728(92)90026-h
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发表时间:
1992-01-01
影响因子:
3.3
通讯作者:
HART, MN
HART, MN
中科院分区:
医学4区
文献类型:
--
作者:
FABRY, Z;WALDSCHMIDT, MM;HART, MN

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中枢神经系统中免疫反应的启动机制知之甚少。在这份报告中,我们描述了存在的细胞间粘附分子-1(ICAM-1)和Lgp 55(建议小鼠同源的人细胞间粘附分子-2,ICAM-2)的脑微血管内皮(EN)细胞的表面上,并显示在体外诱导ICAM-1分子EN细胞与促炎细胞因子。用生物素标记的抗ICAM-1抗体(YN 1/1.7.4)流式细胞术检测ICAM-1表达。用PA 3单克隆抗体鉴定Lgp 55表达。根据我们的结果,30-40%的未活化的脑EN细胞表达ICAM-1,15-20%表达Lgp 55分子。ICAM-1分子表达在用重组鼠γ干扰素(IFN-γ)、肿瘤坏死因子(TNF-α)和白细胞介素-1-α(IL-1-α)以剂量依赖性方式激活细胞后增加。ICAM-1的表达在细胞因子处理后2 h即开始增加,24 h后达到高峰。转化生长因子-β(TGF-β)对ICAM-1分子表达无影响。Lgp 55分子似乎不受促炎细胞因子的调节。ICAM-1和Lgp 55的表达被发现是极化的管腔表面的EN通过共聚焦激光显微镜表明白细胞的可及性。诱导型ICAM-1表达可能在中枢神经系统内炎症反应的形成中起关键作用。
The mechanisms for the initiation of immune reactions in the central nervous system are poorly understood. In this report, we describe the presence of intercellular adhesion molecule-1 (ICAM-1) and Lgp 55 (suggested mouse homologue of human intercellular adhesion molecule-2, ICAM-2) on the surface of brain microvessel endothelium (EN) cells and show in vitro induction of ICAM-1 molecules on EN cells with pro-inflammatory cytokines. ICAM-1 expression was detected using flow cytometry analysis with biotinylated anti-ICAM-1 antibody (YN1/1.7.4). Lgp 55 expression was characterized using PA3 monoclonal antibody. According to our results, 30-40% of the non-activated brain EN cells expressed ICAM-1 and 15-20% expressed Lgp 55 molecules. The ICAM-1 molecule expression was increased after the activation of the cells with recombinant murine gamma interferon (IFN-gamma), tumor necrosis factor (TNF-alpha), and interleukin-1-alpha (IL1-alpha) in a dose-dependent manner. The increased ICAM-1 expression was detected as early as 2 h following the cytokine treatment and reached its maximum after 24 h. Transforming growth factor-beta (TGF-beta) did not influence the expression of ICAM-1 molecule. Lgp 55 molecule does not seem to be regulated by pro-inflammatory cytokines. ICAM-1 and Lgp 55 expression was found to be polarized on the luminal surface of EN by confocal laser microscopy suggesting accessibility for leukocytes. Inducible ICAM-1 expression may play a critical role in formation of inflammatory reactions inside the central nervous system.