CELL-PROLIFERATION ON FIBRIN - MODULATION BY FIBRINOPEPTIDE CLEAVAGE

Fibrin forms the cohesive network of hemostatic plugs and thrombi, and it also provides the temporary matrix for initial support of healing and revascularization. Because cell proliferation is needed for revasc ularization after vessel injury, we have characterized structural requ irements of fibrin needed to support cell proliferation on fibrin in v itro, Proliferation of cultured human endothelial cells and fibroblast s was measured by H-3-thymidine incorporation on fibrin surfaces varyi ng in structure. Fibrin prepared with thrombin and lacking both fibrin opeptides A and B (desAB fibrin) supported proliferation of both endot helial cells and fibroblasts. In contrast, fibrin prepared with reptil ase, which cleaves only fibrinopeptide A, supported significantly less proliferation. Also, fibrin prepared by thrombin treatment of fibrino gen lacking residues beta 1-42 supported only a low level of prolifera tion. Therefore, fibrinopeptide B cleavage and exposure of beta 15-42 enhanced proliferation of cells on fibrin. Specific proteolytic inhibi tors were used to eliminate the potential mitogenic effects of residua l fibrin bound thrombin. Additional controls showed that neither catal ytically inactive thrombin nor addition of the thrombin receptor-activ ating peptide (SFLLRNPNDKYEPF [SFLL]) stimulated proliferation on desA fibrin. The results indicate that cell proliferation on fibrin is enh anced by fibrinopeptide B cleavage and exposure of the amino terminus of the fibrin beta chain. They also show that specific structural feat ures of the temporary fibrin matrix formed at sites of injury may modu late the proliferative response of vascular cells. (C) 1995 by The Ame rican Society of Hematology.