Our purpose is to study the monocyte in immunologically induced glomerulonephritis. We have outlined four areas of investigation. The first considers possible cellular and humoral mechanisms responsible for inducing monocyte infiltration into glomeruli. In order to assess the role of lymphocyte mediation, we have developed an experimental model of glomerulonephritis utilizing a hapten, azobenzenearsonate (ABA), that has the distinctive property of evoking selective T cell reactivity under appropriate immunizing conditions. The hapten is planted in the glomerulus of immune animals by intravenous injection of nephrotoxic antibody or aggregated gamma globulin, both conjugated to ABA. The model permits an analysis of the relationship among parameters of T cell activation, degree of monocyte infiltration into the glomerulus, and abnormal glomerular function. Using this model, we plan to evaluate the possible interaction between antibody-dependent and cellular mechanisms of glomerular injury, as well as the possible role of suppressor T cells in the control of nephritis. Concurrent studies on humoral mechanisms of monocyte infiltration will be carried out with initial emphasis on the complement system. The second project characterizes the monocytes and macrophages isolated from glomeruli according to the presence or absence of Ia molecules and their capacity to interact with T lymphocytes in culture. We are particularly interested in establishing whether there is a particular subset of monocytes-macrophages in normal or diseased glomeruli capable of mediating the glomerular damage and/or the interaction with the T cells. A third line of investigation examines the monocytes-macrophages isolated from the glomeruli for their synthesis and of various biologically important molecules and for their effects when added to cultures of growing glomerular cells. Finally, we propose attempts to influence or abrogate the effects of monocyte infiltration in glomerulonephritis. Interventions include the use of drugs known to affect mononuclear cell function and antisera specific for Ia molecules.
