The integrin VLA-4 supports tethering and rolling in flow on VCAM-1.
The integrin VLA-4 supports tethering and rolling in flow on VCAM-1.
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DOI：
10.1083/jcb.128.6.1243
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发表时间：
1995-03
期刊：
影响因子：
--
通讯作者：
Springer TA
中科院分区：
文献类型：
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作者：
Alon R;Kassner PD;Carr MW;Finger EB;Hemler ME;Springer TA
此前已有研究表明，选择素可以将流动的白细胞拴在血管壁上，并调节滚动。在这里，我们报告集成VLA-4也可以支持系留和滚动。血液T淋巴细胞和α4整合素转基因细胞可以在剪切流中锚定，然后通过整合素VLA-4与流室壁上纯化的VCAM-1结合而滚动。VLA-4转染体在肿瘤坏死因子刺激的内皮细胞上表现出类似的捆绑和滚动。系绳效率、滚动速度和抗剥离能力与VCAM-1密度有关。ICAM-1、纤维连接蛋白或纤维连接蛋白片段上没有发生拴系和滚动，并且拴系不需要整合素激活或α4细胞质结构域的存在。整合素激活剂Mn2+、佛波酯和单抗TS2/16可使VCAM-1上的滚动细胞自发停止，和/或由整合素激活剂Mn2+、佛波酯和单抗TS2/16触发。这些整合素激活剂和α4细胞质结构域促进了对剥离的抵抗力。综上所述，结果表明VLA-4是一种多功能的整合素，可以介导对VCAM-1的拴系、滚动和牢固阻止。
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.