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PMID: 7534768 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of cell biology ·Vol. 128 ·No. 6 ·1995-03-00 ·Pages 1243-53

Alon R, Kassner PD, Carr MW, Finger EB, Hemler ME, Springer TA

Abstract

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.

MeSH Terms
Cell Adhesion Cell Adhesion Molecules/metabolism Cell Line, Transformed Endothelium, Vascular/metabolism Humans Receptors, Very Late Antigen/metabolism T-Lymphocytes/metabolism Vascular Cell Adhesion Molecule-1
Chemicals
Cell Adhesion Molecules Receptors, Very Late Antigen Vascular Cell Adhesion Molecule-1
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Alon R
Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115.
Kassner P D
Carr M W
Finger E B
Hemler M E
Springer T A
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.128.6.1243
Published
1995-03-00
Pages
1243-53
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2120426
Subset
IM
Grants
NIGMS NIH HHS · GM46526 · United States
NHLBI NIH HHS · HL48675 · United States
External Links
PubMed source DOI: 10.1083/jcb.128.6.1243 PMC Full Text View journal details
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