Mononuclear phagocytes play important effector roles in chronic pathological inflammation responses to obligate facultative intracellular pathogens, tumors, and toxic agents. They also participate in the process of antigen-presentation in immunocompetent cells. In these respective processes mononuclear phagocytes interact in vivo with lymphocytes and their products in a manner which is poorly understood. It has recently become apparent that: 1) lymphocytes and macrophages synthesize proteins of the serum complement system; 2) lymphoblastoid cells activate complement; and, 3) complement activation fragments induce functional changes in mononuclear phagocytes which may mimic the effects of MIF, chemotactic factor, and MAC in vitro. These findings raise a question concerning the possible role of leukocyte synthesized complement proteins as mediators of cellular immunity in tissue reactions of chronic inflammation. It is the purpose of the present request for research support to study: (1) The effects induced by treatment of mononuclear phagocytes with complement activation fragments, i.e. do these agents play a role in the processes by which monocytes are induced to """"""""mature"""""""", and/or become """"""""activated"""""""" to increased bactericidal activity? (2) The activation and synthesis of complement proteins (Factor B and C5) by lymphocytes and macrophages obtained from sites of chronic inflammation, i.e. do """"""""activated"""""""" macrophages and/or immunologically committed lymphocytes obtained from chronic inflammatory sites activate complement? (3) The extent to which complement proteins, synthesized and secreted by human peripheral blood lymphocytes or monocytes, may play a role in vitro as lymphokines or monokines.
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