THE CONVERSION OF FIBRINOGEN TO FIBRIN - RECOMBINANT FIBRINOGEN TYPIFIES PLASMA-FIBRINOGEN

Plasma fibrinogen is a mixture of multiple molecular forms arising mai nly through alternative mRNA processing and subsequent posttranslation al modification. Recombinant fibrinogen is synthesized without alterna tive mRNA processing in a cultured cell system that may generate novel posttranslational modifications. Thus, to show that recombinant fibri nogen can serve as a functional model for plasma fibrinogen, we have e xamined the conversion of fibrinogen to fibrin, comparing the recombin ant with the plasma protein, We examined the kinetics of (1) thrombin- catalyzed fibrinopeptide release, (2) thrombin-catalyzed polymerizatio n of fibrinogen, (3) the polymerization of fibrin monomers, and (4) FX IIIa-catalyzed cross-link formation. We saw small differences in polym erization, suggesting that the ordered assembly of protofibrils and fi bers was not identical, In all other analyses, we found that plasma fi brinogen and recombinant fibrinogen were remarkably similar. Using ele ctron microscopy, we examined the structures of individual fibrinogen molecules and fibrin clots. Individual fibrinogen molecules were predo minantly three nodule structures for both recombinant and plasma prote ins, Both samples also displayed four nodule structures, but fewer fou r nodule structures were found with recombinant fibrinogen. Fibrin clo t structures were essentially indistinguishable. We concluded that rec ombinant fibrinogen can serve as a accurate model for plasma fibrinoge n. (C) 1997 by The American Society of Hematology.