We propose that immunologic and viral injury of endothelial cells plays an important role in the development of a number of vessel wall disorders including some cases of vasculitis and thrombosis. During this grant period we will determine whether the sera of patients with four types of inflammatory vascular disorders (systemic lupus, scleroderma, Henoch-Schonlein purpura and IgA nephropathy) contain specific anti-endothelial cell antibodies or immune complexes which are capable of binding to the endothelium. We will determine the serologic characteristics of these antibodies and their capacity to activate the complement system. We will also determine whether these sera contain immune complexes which bind to the Fc receptor expressed on endothelial cells. We will determine if endothelial cells can internalize surface-bound immune complexes via these Fc receptors. Alternatively, endothelial cells may acquire a phagocytic capcity following the induction of viral Fc and C3 receptors by infection with Herpes Simplex Type I. We will also ask if endothelial cells can lyse IgG-coated platelets bound to these surface Fc receptors. We will also determine if anti-endothelial cell antibodies, or other injurious plasma factors, are present in the plasma of patients with four types of thrombotic disorders (thrombotic thrombocytopenic purpura, eclampsia, heparin-associated thrombocytopenia/thrombosis, and patients with "lupus anticoagulants"). We will determine whether such antibodies cause the endothelial cells to become a thrombogenic surface by altering the production of tissue factor, plasminogen activator, inhibitors of plasminogen activator and cause the adherence and activation of platelets. The effect of certain infections of endothelial cells on these processes will be studied as well.