Dore-Duffy P, Balabanov R, Washington R, Swanborg R H
Wayne State University Multiple Sclerosis Research Center, Department of Neurology, Detroit, MI.
Mol Chem Neuropathol. 1994 Aug;22(3):161-75. doi: 10.1007/BF03160103.
Postcapillary endothelium at the sites of inflammation undergoes a series of changes collectively termed endothelial cell activation. Activated endothelium expresses immunologically relevant surface proteins that include MHC class II antigens (Ags) and adhesion proteins, as well as exhibits a number of functional changes. Endothelial activation has not been thoroughly studied in CNS endothelium. We have examined cytokine-mediated endothelial activation in isolated rat CNS microvessels. Freshly isolated rat CNS microvessels are viable in culture for at least 72 h. Untreated microvessels express no endothelial activation antigens, but do exhibit constitutive expression of the transferrin receptor (tfR). INF gamma induces a dose-dependent increase in both MHC class II antigens and tfR measured by immunofluorescent staining and quantitated by laser cytometry. IFN gamma-mediated endothelial cell activation could be inhibited with as little as 2 ng/mL TGF-beta 1. although 100% inhibition was seen with 10 ng/mL TGF-beta 1. Cytokine-preactivated endothelial expression of class II Ag and tfR could also be inhibited by TGF-beta 1. TGF-beta 1-treated microvessels become anergic to IFN gamma stimulation. Results suggest that TGF-beta 1 may have a regulatory role in endothelial activation.
炎症部位的毛细血管后内皮会经历一系列变化，这些变化统称为内皮细胞活化。活化的内皮表达包括MHC II类抗原（Ags）和黏附蛋白在内的免疫相关表面蛋白，并且还表现出一些功能变化。中枢神经系统内皮中的内皮活化尚未得到充分研究。我们已经在分离的大鼠中枢神经系统微血管中研究了细胞因子介导的内皮活化。新鲜分离的大鼠中枢神经系统微血管在培养中至少存活72小时。未经处理的微血管不表达内皮活化抗原，但确实表现出转铁蛋白受体（tfR）的组成性表达。通过免疫荧光染色测量并用激光细胞仪定量，INFγ诱导MHC II类抗原和tfR的剂量依赖性增加。仅2 ng/mL的TGF-β1就能抑制IFNγ介导的内皮细胞活化，不过10 ng/mL的TGF-β1可实现100%抑制。TGF-β1也能抑制细胞因子预活化的内皮细胞II类Ag和tfR的表达。经TGF-β1处理的微血管对IFNγ刺激变得无反应。结果表明，TGF-β1可能在内皮活化中起调节作用。
