PLATELET AND FIBRIN DEPOSITION AT THE DAMAGED VESSEL WALL - COOPERATIVE SUBSTRATES FOR NEUTROPHIL ADHESION UNDER FLOW CONDITIONS

At sites of vessel wail damage, the primary hemostatic reaction involv es platelet and fibrin deposition. At these sites, circulating leukocy tes marginate and become activated. Adhered platelets can support leuk ocyte localization; however, the role of fibrin in this respect is not known. We studied the adhesion of human neutrophils (polymorphonuclea r leukocytes [PMNs]) to endothelial extracellular matrix (ECM)bound fi brin and platelets under flow conditions. ECM alone did not show PMN a dhesion. ECM-coated cover slips were perfused with plasma to form a su rface-bound fibrin network, and/or with whole blood to allow platelet adhesion. Unstimulated PMNs adhered to fibrin at moderate shear stress (20 to 200 mPa). ECM-bound platelets induced rolling adhesion and all owed more PMNs to adhere at higher shear (320 mPa). ECM coated with bo th platelets and fibrin induced more static and shear-resistant PMN ad hesion. PMN adhesion to fibrin alone but not to platelet/fibrin surfac es was inhibited by soluble fibrinogen. Adhesion to fibrin alone was i nhibited by CD1 and CD18 blocking antibodies. Furthermore, fibrin form ed under flow conditions showed up to threefold higher PMN adhesion co mpared with fibrin formed under static conditions, due to structural d ifferences. These results indicate that circulating PMNs adhere to fib rin in an integrin-dependent manner at moderate shear stresses. Howeve r, at higher shear rates (>200 mPa), additional mechanisms tie, activa ted platelets) are necessary for an interaction of PMNs with a fibrin network. (C) 1997 by The American Society of Hematology.