Dore-Duffy P, Washington R A, Balabanov R
Wayne State University School of Medicine, Department of Neurology, Detroit, Michigan 48201.
J Cereb Blood Flow Metab. 1994 Sep;14(5):837-44. doi: 10.1038/jcbfm.1994.105.
Much of what is known of endothelial responses to cytokines has been derived from in vitro studies using cultured human umbilical vein endothelial cells (EC). Less is known of CNS EC responses and whether intact endothelium responds similarly to cultured cells. We have used techniques by which rat CNS microvessels can be isolated, then cultured in vitro, to study the response of intact endothelium to activation with cytokines. These microvessels are composed of viable EC and perivascular cells, predominantly pericytes. Expression of EC activation antigens in multicellular systems such as cultured microvessels can be assessed quantitatively using immunofluorescence laser cytometry. Interferon gamma increased immunologically reactive major histocompatibility complex class II antigens (< 300 to 2,398 +/- 225 average fluorescence intensity), while tumor necrosis factor alpha induced an increase in vascular cell adhesion molecule-1 (2,167 +/- 171) and E-selectin (1,628 +/- 315). CNS EC appeared to respond similarly to cultured EC with the exception that E-selectin expression was not transiently expressed but was maintained by microvessel EC for 24 and 48 h. Cultured CNS microvessels provide a good system for studying EC activation.
目前已知的内皮细胞对细胞因子的反应,大多来自于使用培养的人脐静脉内皮细胞(EC)进行的体外研究。对于中枢神经系统内皮细胞的反应以及完整的内皮细胞是否与培养细胞有相似反应,我们了解得较少。我们采用了一些技术,通过这些技术可以分离大鼠中枢神经系统微血管,然后在体外进行培养,以研究完整内皮细胞对细胞因子激活的反应。这些微血管由存活的内皮细胞和血管周细胞(主要是周细胞)组成。在多细胞系统(如培养的微血管)中,内皮细胞激活抗原的表达可以使用免疫荧光激光细胞术进行定量评估。γ干扰素增加了免疫反应性主要组织相容性复合体II类抗原(平均荧光强度从<300增加到2398±225),而肿瘤坏死因子α则诱导血管细胞黏附分子-1(2167±171)和E-选择素(1628±315)增加。中枢神经系统内皮细胞的反应似乎与培养的内皮细胞相似,不同之处在于E-选择素的表达不是短暂表达,而是由微血管内皮细胞维持24小时和48小时。培养的中枢神经系统微血管为研究内皮细胞激活提供了一个良好的系统。