The integrin alpha9beta1 mediates adhesion to activated endothelial cells and transendothelial neutrophil migration through interaction with vascular cell adhesion molecule-1.
The integrin alpha9beta1 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 alpha4beta1, in the inducible endothelial ligand, vascular cell adhesion mole-cule-1 (VCAM-1). We therefore sought to determine whether alpha9beta1 also recognizes VCAM-1, and whether any such interaction would be biologically significant. In this report, we demonstrate that alpha9beta1 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 alpha9beta1 is highly and selectively expressed on neutrophils and is critical for neutrophil migration on VCAM-1 and tenascin-C. Finally, alpha9beta1 and alpha4 integrins contribute to neutrophil chemotaxis across activated endothelial monolayers. These observations suggest a possible role for alpha9beta1/VCAM-1 interactions in extravasation of neutrophils at sites of acute inflammation.
Taooka
Y
Y
Lung Biology Center, Center for Occupational and Environmental Health, Cardiovascular Research Institute and the Department of Medicine, University of California, San Francisco, California 94143, USA.
Chen
J
J
Yednock
T
T
Sheppard
D
D
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D039001:Integrin alpha Chains; D039441:Integrin alpha4; D016023:Integrins / Q000235:genetics / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology; D014162:Transfection; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000494:pharmacology / Q000502:physiology*
D015703:Antigens, CD; D039001:Integrin alpha Chains; D016023:Integrins; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; C113256:integrin alpha 9 beta 1; C084613:integrin alpha9; D039441:Integrin alpha4