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

Research output: Contribution to journalArticle

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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 - Mar 27 1995

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Integrin alpha4beta1
Vascular Cell Adhesion Molecule-1
Integrins
Fibronectins
Selectins
Phorbol Esters
Intercellular Adhesion Molecule-1
Endothelium
Leukocytes
T-Lymphocytes

Cite this

Alon, R., Kassner, P. D., Carr, M. W., Finger, E. B., Hemler, M. E., & Springer, T. A. (1995). The integrin VLA-4 supports tethering and rolling in flow on VCAM-1. Journal of Cell Biology, 128(6), 1243-1253. https://doi.org/10.1083/jcb.128.6.1243

The integrin VLA-4 supports tethering and rolling in flow on VCAM-1. / Alon, R.; Kassner, P. D.; Carr, M. W.; Finger, E. B.; Hemler, M. E.; Springer, T. A.

In: Journal of Cell Biology, Vol. 128, No. 6, 27.03.1995, p. 1243-1253.

Research output: Contribution to journalArticle

Alon, R, Kassner, PD, Carr, MW, Finger, EB, Hemler, ME & Springer, TA 1995, 'The integrin VLA-4 supports tethering and rolling in flow on VCAM-1', Journal of Cell Biology, vol. 128, no. 6, pp. 1243-1253. https://doi.org/10.1083/jcb.128.6.1243
Alon, R. ; Kassner, P. D. ; Carr, M. W. ; Finger, E. B. ; Hemler, M. E. ; Springer, T. A. / The integrin VLA-4 supports tethering and rolling in flow on VCAM-1. In: Journal of Cell Biology. 1995 ; Vol. 128, No. 6. pp. 1243-1253.
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