Human neutrophil integrin α9β1: up-regulation by cell activation and synergy with β2 integrins during adhesion to endothelium under flow

Neutrophil beta 1 integrin expression and contribution to cell adhesion were revisited in this study. alpha 9 beta 1 and alpha 5 beta 1 appeared here as the main beta 1 integrins expressed on the membrane of resting platelet-depleted neutrophils-alpha 6 beta 1 representing <15% and alpha 2 beta 1 undetectable. Neutrophil activation slightly enhanced alpha 5 expression, did not change alpha 6, but resulted in a two- to threefold increase of alpha 9 beta 1, which then became the major beta 1 integrin of the neutrophil membrane. alpha 9 beta 1 was the only beta 1 integrin to be up-regulated after transendothelial migration across TNF-alpha-activated HUVECs. As alpha 9 beta 1 binds VCAM-1, we analyzed its participation to neutrophil adhesion to TNF-alpha-activated endothelial cells. Blocking anti-alpha 9 mAb had little effect on neutrophil static adhesion, contrasting with the strong inhibition by anti-beta 2 mAb. Under flow conditions, the anti-alpha 9 mAb had no effect by itself on neutrophil adhesion to activated HUVECs but enhanced the blocking effect of anti-beta 2 antibodies significantly and further enhanced the velocity of beta 2-blocked rolling neutrophils. In conclusion, we describe here for the first time a nearly exclusive up-regulation of alpha 9 beta 1 expression among all beta 1 integrins during neutrophil activation and transendothelial migration and a possibly important synergy between alpha 9 beta 1 and beta 2 integrins in stabilizing neutrophil adhesion to endothelium under flow conditions. J. Leukoc. Biol. 88: 321-327; 2010.