Vascular endothelial cells at sites of cell-mediated immune responses show morphological alteration, expression of new antigens and acquisition of new functions. The endothelial activation response may be studied in vitro by addition of specific immune-generated mediators (i.e. lymphokines) to cultured endothelial cells. To date, different mediators have been found to produce distinct but overlapping patterns of activation through the expression of specific genes. The long term goals of this proposal are to fully determine the patterns of activation of endothelial cells by different lymphokines and to delineate the genetic mechanisms of these activation processes. In the proposed experiments, available and de novo generated monoclonal antibodies will be used to define activation patterns; and available and de novo generated cDNA probes will be used to delineate genetic mechanisms. Two specific activation antigens will be studied in detail: the molecule identified by monoclonal antibody H4/18 (an acute activation antigen), and the T cell recognition molecules encoded for by the major histocompatibility complex (which appear to rise with chronic activation). The anticipated results of these studies include the development of a panel of probes (antibody and cDNA) which can be used to analyze endothelial cell activation in vitro and in situ. These experiments should also provide a better understanding of specific activation pathways. Finally, the availability of such reagents and data may suggest new avenues for therapeutic intervention aimed at blocking harmful immune inflammatory episodes through modulation of endothelial cell responses.
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