© The Rockefeller University Press,
0021-9525/1999//413 $5.00
The Journal of Cell Biology, Volume 145, Number 2,
, 1999 413-420
The Integrin
9β1 Mediates Adhesion to Activated Endothelial Cells and Transendothelial Neutrophil Migration through Interaction with Vascular Cell Adhesion Molecule-1
Yasuyuki Taooka*,
John Chen*,
Ted Yednock
, and
Dean Sheppard*
* Lung Biology Center, Center for Occupational and Environmental Health, Cardiovascular Research Institute and the Department of Medicine, University of California, San Francisco, California 94143; and
Elan Pharmaceuticals, South San Francisco, California 94080
The integrin
9β1 has been shown to be widely expressed on smooth muscle and epithelial cells, and to mediate adhesion to the extracellular matrix proteins osteopontin and tenascin-C. We have found that the peptide sequence this integrin recognizes in tenascin-C is highly homologous to the sequence recognized by the closely related integrin
4β1, in the inducible endothelial ligand, vascular cell adhesion mole-cule-1 (VCAM-1). We therefore sought to determine whether
9β1 also recognizes VCAM-1, and whether any such interaction would be biologically significant. In this report, we demonstrate that
9β1 mediates stable cell adhesion to recombinant VCAM-1 and to VCAM-1 induced on human umbilical vein endothelial cells by tumor necrosis factor-
. Furthermore, we show that
9β1 is highly and selectively expressed on neutrophils and is critical for neutrophil migration on VCAM-1 and tenascin-C. Finally,
9β1 and
4 integrins contribute to neutrophil chemotaxis across activated endothelial monolayers. These observations suggest a possible role for
9β1/VCAM-1 interactions in extravasation of neutrophils at sites of acute inflammation.
Key Words: integrin
9β1
4 neutrophil migration vascular cell adhesion molecule-1
Abbreviations used in this paper: EGM, endothelial cell growth media; FMLP, formyl-methionylleucylphenylalanine; HUVE, human umbilical vein endothelial; ICAM, intercellular adhesion molecule; IFN, interferon; TNF, tumor necrosis factor; VCAM-1, vascular cell adhesion molecule-1.

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