Factors relevant to stimulatory activity of fibrin degradation products in vivo.

Extracts of atherosclerotic lesions contain a range of fibrin degradation products (FbDP), similar fragments have been detected in extracts from human and mouse healing skin wounds and from the invasive edge of human breast carcinomas, which are all proliferating systems. We have previously shown that FbDP stimulate cell proliferation including angiogenesis in the chick chorioallantoic membrane (CAM), and sought to characterize further the active components. Fibrin prepared from platelet-rich and platelet-free plasma, and purified Kabi fibrinogen, was treated with plasmin, and the digests were all active. FbDP from platelet-rich plasma clots also increased vascularity of the CAM. Prior removal of fibronectin from plasma by gelatin-Sepharose affinity chromatography did not affect proliferative activity. Current studies showed that long digests of fibrin, in which the only major band detectable is fibrin fragment E are active. Commercial fibrinogen derived fragment E, itself inactive on the CAM, becomes active after exposure to thrombin cleavage of fibrinopeptides. Recently fragment E has been isolated from shorter digests, by simple filtration through a Millipore 0.2 microns centrifuge filter. It displayed similar activity to the fragment E obtained from long digests. Fragment E in plaque extracts has been shown consistently to lack fibrinopeptide A indicating it is of fibrin origin.