Two broad areas of investigation will be examined in delineating the role of the vascular endothelium in the potential immunopathogenesis of vasculitis. Experimental models of endothelial cell function will be established with the idea of eventually using such models to study regulatory factors in vasculitis. The endothelial cell will be studied for its ability to modulate immune cell function in various ways, such as the ability of endothelial cells to serve as accessory cells for lymphocyte activation and the capacity of endothelial cells to produce immunoregulatory molecules such as interleukin-1. In particular, the regulation of IL-1 production by endothelium cells by immune and inflammatory mediators, as well as factors from vasculitic patient's sera and cells will be studied in depth. The expression of immunological cell surface markers by endothelial cells will also be studied and their relationship to and modulation by factors related to clinically active vasculitis. Endothelial cells will also be examined as a potential target for injury in vasculitis by concentrating on the potential antigenicity of endothelial cell plasma membrane proteins such as angiotensin-1-converting enzyme and lipoprotein lipase. The role of cell mediated immunity to endothelial cells and cell mediated immunity directed to basement membrane collagen will also be studied. These proposed experiments may shed new and exciting information on the potential immunopathogenesis of necrotizing vasculitis. A better understanding of the mechanism of vascular injury in vasculitis should lead to a more rational approach to the therapy of patients with this widely varied disorder.
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