Inflammatory mechanisms are important in the pathogenesis of diseases throughout clinical medicine. To develop a further understanding of these diseases and allow improved diagnosis and treatment, we propose a program project entitled """"""""Molecular and Cellular Mechanisms of Human Inflammatory Diseases."""""""" This program project will be comprised of a series of highly collaborative and interactive projects with a clinical focus on inflammatory eye disease. These conditions are prevalent among systemic inflammatory diseases and illustrate well the involvement of major effector systems in inflammation. The pathogenetic and functional properties of various cell types in these ocular disorders will be investigated in conjunction with efforts to develop novel approaches to therapy. Reflecting this clinical focus, three closely related projects will investigate the role of the monocyte in inflammatory disease. These projects will explore the phenotypic and functional properties of monocyte-derived giant cells; the modification of murine mononuclear phagocyte cell function by monoclonal antibodies; and the biochemical processes in monocyte function as revealed by a series of novel purine nucleoside analogs. The program project will also investigate the immunochemical properties of a group of antibodies termed poly-specific. These antibodies bind more than one target antigen and mediate inflammatory damage by diverse effector mechanisms. The techniques of molecular cloning will be used to produce highly purified antigens of known sequence to define more precisely the nature of these binding interactions. Together, these studies unite clinical and basic investigators with a common interest in inflammation and immuno-regulation and provide a mechanism for expanding their research into novel and clinically relevant directions.
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