PLATELET-ASSOCIATED FIBRINOGEN AND ICAM-2 INDUCE FIRM ADHESION OF NEUTROPHILS UNDER FLOW CONDITIONS

Surface-bound platelets support selectin-mediated rolling and beta(2)- integrin-mediated firm adhesion of neutrophils (PMN) under flow condit ions. We examined which ligands on platelets mediate this firm adhesio n. Surface-bound platelets express ICAM-2 and GPIIbIIIa-bound fibrinog en, which are ligands for LFA-I and MAC-I. In a well defined model for vessel wall injury, blood from an afibrinogenemic patient was perfuse d over ECM-coated coverslips to obtain fibrinogen-free platelet surfac es. At high shear rates, PMN-adhesion to fibrinogen-free platelet surf aces decreased compared to fibrinogen-containing controls. Under these conditions, firm adhesion and not rolling was blocked demonstrating t he importance of fibrinogen in this process. In addition, MAC-1 and LF A-1 on PMN and ICAM-2 on platelets played a role in firm adhesion; the effect of blocking antibodies was most evident at high shear. The eff ects of fibrinogen depletion and ICAM-2 blocking were additive. In con clusion, multiple redundant ligands, like ICAM-2 and fibrinogen, induc e firm and shear resistant PMN adhesion to platelets under flow condit ions. Individually these ligands become critical at higher shear. Bloc king of two Or more interactions also interferes with low shear adhesi on.