ADHESION OF PLATELETS TO SURFACE-BOUND FIBRINOGEN UNDER FLOW

After platelet activation, fibrinogen mediates platelet-platelet inter actions leading to platelet aggregation, In addition, fibrinogen can a lso function as a cell adhesion molecule, providing a substratum for a dhesion of platelets and endothelial cells. In this report, we studied the adhesion of platelets to surface-immobilized fibrinogen under flo w in different shear rates. Heparinized whole blood containing mepacri ne-labeled platelets was perfused for two minutes at various wall shea r rates from 250 to 2,000 s(-1) in a parallel plate flow chamber. The number of adherent fluorescent platelets was quantitated every 15 seco nds with an epifluorescent videomicroscope and digital image processin g system. When compared with platelet adhesion and aggregation seen on glass surfaces coated with type I bovine collagen, a significant incr ease in platelet adhesion was observed on immobilized fibrinogen up to wall shear rates of 800 s(-1). The adherent platelets formed a single layer on fibrinogen-coated surfaces. Under identical conditions, no s ignificant adhesion was observed on fibronectin- or vitronectin-coated surfaces, Although platelet adhesion to collagen was substantially in hibited by the platelet inhibitors prostaglandin E(1) and theophylline , these inhibitors had no effect on platelet adhesion to fibrinogen. P latelets adhered to recombinant homodimeric wild-type (gamma 400-411) fibrinogen, but not to the recombinant homodimeric gamma' variant of f ibrinogen. Platelet adhesion to recombinant fibrinogen with RGD to RGE mutations at positions alpha 95-97 and alpha 572-574 was similar to t hat with plasma-derived fibrinogen. These results show that platelets adhere to fibrinogen-coated surfaces under moderate wall shear rates, that the interaction is mediated by the fibrinogen 400-411 sequence at the carboxy-terminus of the gamma chain, and that the interaction is independent of platelet activation and the RGD sequences in the alpha chain. (C) 1996 by The American Society of Hematology.