The objective of proposed research is to investigate the mechanism of the interaction of polymerizing fibrin with platelets and with other cells (fibroblasts, red cells and leukocytes), and the biological significance of this interaction. Platelets and undifferentiated fibroblasts adhere to polymerizing fibrin and promote fibrin polymerization but they do not adhere to fully polymerized fibrin. The significance of platelets and fibrin in hemostatic plugs in thrombi has long been appreciated, but it has been assumed that their roles were additive rather than interactive. Specifically the objectives of our project are: (1) identification of component of platelet membranes which does interact with polymerizing fibrin; identification of specific inhibitors of fibrin-platelet reaction; study of the relationship between platelet-fibrin interaction and fibrin clot retraction; (2) physicochemical characterization of polymerizing fibrin in the acting with platelets; (3) comparison of platelet with other cells (fibroblasts, red cells, polymorphonuclear granulocytes) with respect to the interaction with fibrin; (4) study of cell-fibrin interaction in pathological states involving platelets and other cells; (5) effect of polymerizing fibrin on platelets and on other cells in vivo. For the purpose of the study, cells will be isolated from human or animal blood or prepared by tissue culture techniques. BIBLIOGRAPHIC REFERENCES: Nath, N., Lowery, C., Niewiarowski, S. Antigenic and antiheparin properties of human platelet factor 4 (PF4) Blood 45, 537-550, 1975. Stewart, G.J. and Niewiarowski, S., Ultra-structural studies of reptilase - human platelet rich plasma clots. Symposium on thrombin-like enzymes - properties and application. July 15-17, 1975, Trier, Germany.