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© The Rockefeller University Press, 0021-9525/1999//413 $5.00
The Journal of Cell Biology, Volume 145, Number 2, , 1999 413-420


Regular Articles

The Integrin {alpha}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{ddagger}, 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 {ddagger} Elan Pharmaceuticals, South San Francisco, California 94080

The integrin {alpha}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 {alpha}4β1, in the inducible endothelial ligand, vascular cell adhesion mole-cule-1 (VCAM-1). We therefore sought to determine whether {alpha}9β1 also recognizes VCAM-1, and whether any such interaction would be biologically significant. In this report, we demonstrate that {alpha}9β1 mediates stable cell adhesion to recombinant VCAM-1 and to VCAM-1 induced on human umbilical vein endothelial cells by tumor necrosis factor-{alpha}. Furthermore, we show that {alpha}9β1 is highly and selectively expressed on neutrophils and is critical for neutrophil migration on VCAM-1 and tenascin-C. Finally, {alpha}9β1 and {alpha}4 integrins contribute to neutrophil chemotaxis across activated endothelial monolayers. These observations suggest a possible role for {alpha}9β1/VCAM-1 interactions in extravasation of neutrophils at sites of acute inflammation.

Key Words: integrin • {alpha}9β1 • {alpha}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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