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

R. Alon, P. D. Kassner, M. W. Carr, E. B. Finger, M. E. Hemler, T. A. Springer

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608 Scopus citations

Abstract

Selectins have previously been shown to tether a flowing leukocyte to a vessel wall and mediate rolling. Here, we report that an integrin, VLA-4, can also support tethering and rolling. Blood T lymphocytes and α4 integrin- transfected cells can tether in shear flow, and then roll, through binding of the integrin 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 α4 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 α4 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.

Original languageEnglish (US)
Pages (from-to)1243-1253
Number of pages11
JournalJournal of Cell Biology
Volume128
Issue number6
DOIs
StatePublished - 1995

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