The integrin alpha 9 beta 1 mediates adhesion to activated endothelial cells and transendothelial neutrophil migration through interaction with vascular cell adhesion molecule-1

The integrin alpha 9 beta 1 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 4 beta 1, in the inducible endothelial ligand, vascular cell adhesion molecule-1 (VCAM-1), We therefore sought to determine whether alpha 9 beta 1 also recognizes VCA M-1, and whether any such interaction would be biologically significant. In this report, we demonstrate that alpha 9 beta 1 mediates stable cell adhes ion to recombinant VCAM-1 and to VCAM-1 induced on human umbilical vein end othelial cells by tumor necrosis factor-alpha. Furthermore, we show that al pha 9 beta 1 is highly and selectively expressed on neutrophils and is crit ical for neutrophil migration on VCAM-1 and tenascin-C. Finally, alpha 9 be ta 1 and alpha 4 integrins contribute to neutrophil chemotaxis across activ ated endothelial monolayers. These observations suggest a possible role for alpha 9 beta 1/VCAM-1 interactions in extravasation of neutrophils at site s of acute inflammation.