Platelet adhesion to late fibrinogen degradation products.

Abstract

Evidence is emerging for the regulation of platelet function at sites of vascular injury or thrombosis by multiple platelet recognition sites in fibrinogen. This study examined the interaction of platelets with immobilized fibrinogen degradation products, fragments D and E. A 60 kDa D fragment (D60) and 30 kDa fragment E supported the adhesion of activated platelets in a static system, despite the absence of gamma chain 400-411 dodecapeptide and RGD sequences. Moreover, platelet adhesion to these fragments was incompletely inhibited by EDTA. In the absence of divalent cations, ADP-stimulated platelet adhesion to fragments D60 or E constituted 31 +/- 12% and 33 +/- 10% (mean +/- SD,n = 23) of adhesion to intact fibrinogen in the presence of divalent cations, respectively. This EDTA-resistant adhesion was distinctly modulated by thrombin which preferentially supported platelet adhesion to fragment E, and chymotrypsin which selectively supported platelet adhesion to fragment D60. Furthermore, two potent inhibitors of fibrinogen binding, the 10E5 monoclonal antibody directed against the GPIIb-IIIa complex and the RGDF peptide, inhibited EDTA-resistant platelet adhesion to fragment D60 but not to fragment E. These data suggest the presence of novel, non-RGD, non-dodecapeptide containing platelet recognition sequences in both fibrinogen D and E domains which support divalent cation dependent and independent platelet adhesion via potentially unique binding mechanisms.