ICAM-1
内皮干细胞
VCAM-1
细胞生物学
内皮
血脑屏障
生物
效应器
细胞粘附分子
体外
神经科学
生物化学
中枢神经系统
内分泌学
作者
Oliver Steiner,Caroline Coisne,Roméo Cecchelli,Rémy Boscacci,Urban Deutsch,Britta Engelhardt,Ruth Lyck
出处
期刊:Journal of Immunology
[American Association of Immunologists]
日期:2010-09-23
卷期号:185 (8): 4846-4855
被引量:300
标识
DOI:10.4049/jimmunol.0903732
摘要
Abstract Endothelial ICAM-1 and ICAM-2 were shown to be essential for T cell diapedesis across the blood–brain barrier (BBB) in vitro under static conditions. Crawling of T cells prior to diapedesis was only recently revealed to occur preferentially against the direction of blood flow on the endothelial surface of inflamed brain microvessels in vivo. Using live cell-imaging techniques, we prove that Th1 memory/effector T cells predominantly crawl against the direction of flow on the surface of BBB endothelium in vitro. Analysis of T cell interaction with wild-type, ICAM-1–deficient, ICAM-2–deficient, or ICAM-1 and ICAM-2 double-deficient primary mouse brain microvascular endothelial cells under physiological flow conditions allowed us to dissect the individual contributions of endothelial ICAM-1, ICAM-2, and VCAM-1 to shear-resistant T cell arrest, polarization, and crawling. Although T cell arrest was mediated by endothelial ICAM-1 and VCAM-1, T cell polarization and crawling were mediated by endothelial ICAM-1 and ICAM-2 but not by endothelial VCAM-1. Therefore, our data delineate a sequential involvement of endothelial ICAM-1 and VCAM-1 in mediating shear-resistant T cell arrest, followed by endothelial ICAM-1 and ICAM-2 in mediating T cell crawling to sites permissive for diapedesis across BBB endothelium.
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