PLATELET-ADHESION TO LATE FIBRINOGEN DEGRADATION PRODUCTS

Evidence is emerging for the regulation of platelet function at sites of vascular injury or thrombosis by multiple platelet recognition site s in fibrinogen. This study examined the interaction of platelets with immobilized fibrinogen degradation products, fragments D and E. A 60 kDa D fragment (D-60) and 30 kDa fragment E supported the adhesion of activated platelets in a static system, despite the absence of gamma c hain 400-411 dodecapeptide and RGD sequences. Moreover, platelet adhes ion to these fragments was incompletely inhibited by EDTA. In the abse nce of divalent cations, ADP-stimulated platelet adhesion to fragments D-60 or E constituted 31 +/- 12% and 33 +/- 10% (mean +/- SD, n=23) o f adhesion to intact fibrinogen in the presence of divalent cations, r espectively. 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 f ragment D-60. Furthermore, two potent inhibitors of fibrinogen binding , the 10E5 monoclonal antibody directed against the GPIIb-IIa complex and the RGDF peptide, inhibited EDTA-resistant platelet adhesion to fr agment D-60 but not to fragment E. These data suggest the presence of novel, non-RGD, non-dodecapeptide containing platelet recognition sequ ences in both fibrinogen D and E domains which support divalent cation dependent and independent platelet adhesion via potentially unique bi nding mechanisms.