Alon R, Kassner P D, Carr M W, Finger E B, Hemler M E, Springer T A
Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115.
J Cell Biol. 1995 Mar;128(6):1243-53. doi: 10.1083/jcb.128.6.1243.
Selectins have previously been shown to tether a flowing leukocyte to a vessel wall and mediate rolling. Here, we report that an intergrin, VLA-4, can also support tethering and rolling. Blood T lymphocytes and alpha 4 integrin-transfected cells can tether in shear flow, and then roll, through binding of the intergrin VLA-4 to purified VCAM-1 on the wall of a flow chamber. VLA-4 transfectants showed similar tethering and rolling on TNF-stimulated endothelium. Tethering efficiency, rolling velocity, and resistance to detachment are related to VCAM-1 density. Tethering and rolling did not occur on ICAM-1, fibronectin, or fibronectin fragments, and tethering did not require integrin activation or the presence of an alpha 4 cytoplasmic domain. Arrest of rolling cells on VCAM-1 occurred spontaneously, and/or was triggered by integrin activating agents Mn2+, phorbol ester, and mAb TS2/16. These agents, and the alpha 4 cytoplasmic domain, promoted increased resistance to detachment. Together the results show that VLA-4 is a versatile integrin that can mediate tethering, rolling, and firm arrest on VCAM-1.
此前已表明，选择素可使流动的白细胞与血管壁相连并介导滚动。在此，我们报告整合素VLA-4也能支持细胞的黏附与滚动。血液中的T淋巴细胞和转染了α4整合素的细胞能够在剪切流中黏附，然后通过整合素VLA-4与流动腔壁上纯化的血管细胞黏附分子-1（VCAM-1）结合而滚动。VLA-4转染细胞在肿瘤坏死因子刺激的内皮细胞上表现出相似的黏附与滚动。黏附效率、滚动速度和抗脱离能力与VCAM-1的密度有关。在细胞间黏附分子-1（ICAM-1）、纤连蛋白或纤连蛋白片段上未发生黏附与滚动，且黏附不需要整合素激活或α4胞质结构域的存在。滚动细胞在VCAM-1上的停滞自发发生，和/或由整合素激活剂锰离子、佛波酯和单克隆抗体TS2/16触发。这些试剂以及α4胞质结构域可增强抗脱离能力。这些结果共同表明，VLA-4是一种多功能整合素，可介导在VCAM-1上的黏附、滚动和牢固停滞。
