The integrin VLA-4 supports tethering and rolling in flow on VCAM-1.

作者：Ronen Alon, Paul D. Kassner, Michelle Woldemar Carr, Erik B. Finger, Martin E. Hemler, Timothy A. Springer · 发表于：The Journal of Cell Biology · 年份：1995 · DOI：10.1083/jcb.128.6.1243 · 被引用次数：717 · 研究领域：Cell Adhesion Molecules Research、Platelet Disorders and Treatments、Monoclonal and Polyclonal Antibodies Research

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.