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

Abstract

α9β1 is the main β1 integrin of human activated neutrophils; and α9β1/VCAM-1 interactions participate to neutrophilrolling on endothelial cells.Neutrophil β1 integrin expression and contribution to cell adhesion were revisited in this study. α9β1 and α5β1 appeared here as the main β1 integrins expressed on the membrane of resting platelet-depleted neutrophils—α6β1 representing <15% and α2β1 undetectable. Neutrophil activation slightly enhanced α5 expression, did not change α6, but resulted in a two- to threefold increase of α9β1, which then became the major β1 integrin of the neutrophil membrane. α9β1 was the only β1 integrin to be up-regulated after transendothelial migration across TNF-α-activated HUVECs. As α9β1 binds VCAM-1, we analyzed its participation to neutrophil adhesion to TNF-α-activated endothelial cells. Blocking anti-α9 mAb had little effect on neutrophil static adhesion, contrasting with the strong inhibition by anti-β2 mAb. Under flow conditions, the anti-α9 mAb had no effect by itself on neutrophil adhesion to activated HUVECs but enhanced the blocking effect of anti-β2 antibodies significantly and further enhanced the velocity of β2–blocked rolling neutrophils. In conclusion, we describe here for the first time a nearly exclusive up-regulation of α9β1 expression among all β1 integrins during neutrophil activation and transendothelial migration and a possibly important synergy between α9β1 and β2 integrins in stabilizing neutrophil adhesion to endothelium under flow conditions.