The cells of the mononuclear phagocyte system are associated with a wide variety of immune response-related functions and activities. These include a participation in host defense against neoplasia and infectious organisms, and a role in the positive and negative control of immune responses. The potentiation of macrophage activity in the development of such functions is regulated, at least in part, by soluble mediators produced during the course of an immune response. One factor shown to have potent macrophage activating capability is interferon-gamma; however, the mechanisms by which this factor controls macrophage function remain to be elucidate. The objective of the proposed research is to gain an understanding of the molecular basis of macrophage activation, through the immunochemical analysis of cell surface alterations associated with the activation of macrophages by interferon. Using established macrophage cell lines for immunization, xenogeneic monoclonal antibody probes will be developed to cell surface antigens which are induced on macrphages by treatment with immune interferon. These antibodies will then be used in a detailed analysis of the surface antigen phenotype of macrophages at intermediate stages in the pathway of activation, and for identification of specific antigens which play a role in the tumoricidal activity or antigen-presenting cell function of activated cells. The antibodies will also be used, in combination with biochemical techniques, to detect and purify functionally relevant gene products for molecular characterization. Such antibodies ultimately may be useful on a practical level in the selective manipulation of macrophage function in vivo.
