The goal of this research proposal is to study the immunobiology of a mouse-mesangial cell derived factor which has immunological properties. Thus, studies will be done as follows: (a) based on preliminary observations in our laboratory, we have identified a mouse mesangial cell derived immunoregulatory factor which stimulates lymphocyte proliferation by its action on the monocyte/macrophage; also it has been shown that this factor stimulates spleen monocyte/macrophage replication. Further studies are proposed to examine the effect of this factor on monocyte/macrophage function as they relate to inflammation--thus does it stimulate monocyte Interleuken-I release, Ia antigen expression, and how does it modulate monocyte/macrophage production of fibronectin, C5, plasminogen activator production, production of the metabolites of arachidonic acid metabolism, and the expression of Fc receptor activity? Does it posess chemotactant activity for monocytes/macrophages? Studies will also be done to isolate and biochemically characterize the mediators responsible. The information obtained will be fundamental to our knowledge of: (1) how mesangial cells may provide a feedback regulatory loop which modifies the physiology of infiltrating monocytes/macrophages during nephritis; (2) provide a model to study the nature of immunoregulation at a local (tissue specific) level which may have relevance to other areas of cell pathology; (3) identification of a substance which may eventually be used as an immunotherapeutic substance.
