Autologous immune complex nephritis in rats. Influence of modification of mononuclear phagocyte system function.
These studies were designed to determine the effect of modification of mononuclear phagocyte system function on a chronic immune complex disease. Autologous immune complex nephritis in rats (Heymann nephritis) was induced by immunization with renal tubular epithelial antigen (Fx1A). The mononuclear phagocyte system was impaired by splenectomy and stimulated by weekly intraperitoneal injections of zymosan. Serial determinations included 24-hour urinary protein excretion, serum antibody titers, C3, circulating immune complexes, creatinine, and creatinine clearance. Renal tissue was obtained at 21, 42, and 56 days after immunization to evaluate by immunofluorescence the amount of antigen and IgG deposited. Splenectomized rats with Heymann nephritis had significantly greater amounts of glomerular Fx1A antigen and IgG deposits at each time studied than did rats without modification of mononuclear phagocyte system function. Zymosan-treated rats had very few glomerular deposits. In the splenectomized rats, the creatinine clearance was depressed by 50%. All animals had normal levels of C3 and identical antibody titers. In an independent assessment of mononuclear phagocyte system function, plasma clearance of Fx1A was enhanced in zymosan-treated animals and depressed in splenectomized animals. These modifications of mononuclear phagocyte system function were associated with changes in the amount of glomerular deposits of IgG and the clinical course of membranous nephropathy in this animal model. Application of methods for stimulation of mononuclear phagocyte system function may have therapeutic efficacy in the future treatment of human membranous nephropathy.
D000818:Animals; D000917:Antibody Formation; D000936:Antigen-Antibody Complex / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D003176:Complement C3 / Q000276:immunology; D003404:Creatinine / Q000097:blood; D007074:Immunoglobulin G / Q000276:immunology; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000276:immunology; D009393:Nephritis / Q000276:immunology*; D010586:Phagocytes / Q000276:immunology*; D011507:Proteinuria / Q000175:diagnosis; D051381:Rats; D011917:Rats, Inbred Lew; D013156:Splenectomy; D015054:Zymosan / Q000494:pharmacology
D000936:Antigen-Antibody Complex; D003176:Complement C3; D007074:Immunoglobulin G; D015054:Zymosan; D003404:Creatinine