NEUTROPHILS CAN ADHERE VIA ALPHA(4)BETA(1)-INTEGRIN UNDER FLOW CONDITIONS

In this study we investigated the possibility that an alternative path way exists for neutrophil recruitment, namely an alpha(4) beta(1)-depe ndent pathway. A parallel plate chamber was used to investigate whethe r neutrophils could tether, roll, and adhere to tumor necrosis factor alpha (TNF-alpha)-stimulated endothelium via alpha(4) beta(1).alpha(4) beta(1)-integrin was induced on neutrophils using dihydrocytochalasin B and either an endogenous (endothelial-derived) chemotactic agent or an exogenous chemotactic molecule. alpha(4) beta(1)-expressing neutro phils could stably adhere under shear force (2 dyne/cm(2)) to TNF alph a-stimulated endothelium independent of the beta(2)-integrin. The firm adhesion was entirely abolished by antibodies directed against either the alpha(4) or beta(1)-integrin subunits. However, the rolling inter action was not dependent on alpha(4) beta(1) but was abolished by anti selectin therapy. Neutrophils expressing alpha(4) beta(1), could also tether to the endothelium in the presence of antiselectin therapy, but at shear stresses less than 2 dyne/cm(2).alpha(4) beta(1)-expressing neutrophils also tethered to and stably adhered (no rolling) to VCAM-1 - but not to ICAM-1-transfected L cells. The interaction only occurred at shear stress less than 2 dyne/cm(2). A cell line (Ramos) known to express high quantities of alpha(4) beta(1)-integrin interacted with V CAM-1-transfected L cells at very similar shear conditions. alpha(4) b eta(1)-expressing neutrophils were also able to adhere to a second alp ha(4)-integrin ligand, fibronectin; however, this interaction only occ urred under static conditions. These data suggest that, under certain conditions, neutrophils can adhere independently of the beta(2)-integr in pathway and adhere via the alpha(4) beta(1)-integrin. This study re futes the concept that alpha(4) beta(1)-integrin adhesion is restricte d to mononuclear leukocytes and is not functional on human neutrophils . (C) 1997 by The American Society of Hematology.