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

doi:10.1083/jcb.128.6.1243

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

R Alon, PD Kassner, MW Carr, EB Finger, ME Hemler and TA Springer
Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115.

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.
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Huo, Y., Hafezi-Moghadam, A., Ley, K. (2000). Role of Vascular Cell Adhesion Molecule-1 and Fibronectin Connecting Segment-1 in Monocyte Rolling and Adhesion on Early Atherosclerotic Lesions. Circ. Res. 87: 153-159 [Abstract] [Full Text]
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Dong, Z. M., Brown, A. A., Wagner, D. D. (2000). Prominent Role of P-Selectin in the Development of Advanced Atherosclerosis in ApoE-Deficient Mice. Circulation 101: 2290-2295 [Abstract] [Full Text]
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