A broadly based program examining the function of mononuclear phagocytes (MP's) under in vivo and in vitro conditions and focussed on our ability to modulate their role as effector cells in a wide variety of cell mediated reactions. Studies will characterize the cell surface molecules of developmental forms and activated populations by chemical and immunological techniques including the use of monoclonal antibodies. The role of these forms as suppressor cells of B and T lymphocyte mediated reactions and lymphokine production is being evaluated. Model infections with T. cruzi, Toxoplasma gondii and BCG are used to assay the mechanisms by which MP's dispose of various intracellular pathogens. Related studies are characterizing extracellular cytocidal influences on both normal and neoplastic cells. The role of oxygen intermediates in both intracellular and extracellular effector mechanisms is under study as is the nature and influence of secretory molecules, with emphasis on prostaglandins and neutral hydrolases, on inflammation. Detailed studies are underway on the determinants of endocytosis and phagosome-lysosome fusion. The nature of interiorized plasma membrane, its longevity and its recycling back to the cell surface is being evaluated with novel labeling methods which allow us to characterize the vacuoles involved in fluid phase pinocytosis, adsorptive pinocytosis and phagocytosis. Both the polypeptides and lipid moieties of the vacuolar apparatus membranes are under consideration.
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