We completed a number of studies presenting evidence that fibrinogen and fibrin play a major role in the formation of hemostatic plug and tissue repair. We described binding of polymerizing fibrin monomers to platelets and to fibroblasts which results in cell aggregation and clot retraction. We demonstrated that fibrinogen does not bind to intact platelets and that stimulation of platelets either with ADP or their treatment with proteolytic enzymes exposes two classes of fibrinogen receptors. We propose that binding of fibrinogen to high affinity receptors results in platelet aggregation by a mechanism in which adjacent platelets are linked by calcium-fibrinogen bridges. The objectives of our project are: 1) further development and characterization of polyclonal and monoclonal antibodies which interact with fibrinogen receptors on platelet surface and block platelet aggregation; 2) purification of fibrinogen receptors from platelet membranes; 3) characterization of the interaction between fibrinogen and its platelet receptors at the cellular level and in the purified system; 4) comparison of the interaction between platelet fibrinogen and plasma fibrinogen with the platelet receptors; 5) identification of the regions of fibrinogen molecule with interacts with the fibrinogen receptor; 6) identification of the fibrin binding sites on platelet surface and their relationship to fibrinogen receptor; 7) study of the significance of fibrinogen receptor in platelet dependent fibrin clot retraction; 8) attempt to identify fibrinogen/fibrin binding sites on human skin fibroblasts and endothelial cells. Our study could contribute to the understanding of the basic mechanisms involved in hemostasis, thrombosis and tissue repair and their abnormalities in diseases.
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