Neutrophils can adhere via alpha(4)beta(1)-integrin under flow conditions

In this study we investigated the possibility that an alternative pathway exists for neutrophil recruitment, namely an alpha(4) beta(1)-dependent pathway. A parallel plate chamber was used to investigate whether 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 neutrophils could stably adhere under shear force (2 dyne/cm(2)) to TNF alpha-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 interaction was not dependent on alpha(4) beta(1) but was abolished by antiselectin 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 VCAM-1-transfected L cells at very similar shear conditions. alpha(4) beta(1)-expressing neutrophils were also able to adhere to a second alpha(4)-integrin ligand, fibronectin; however, this interaction only occurred under static conditions. These data suggest that, under certain conditions, neutrophils can adhere independently of the beta(2)-integrin pathway and adhere via the alpha(4) beta(1)-integrin. This study refutes the concept that alpha(4) beta(1)-integrin adhesion is restricted to mononuclear leukocytes and is not functional on human neutrophils. (C) 1997 by The American Society of Hematology.