Immune complex induced glomerular lesions in C5 sufficient and deficient mice.
The role in the pathogenesis of immune complex-mediated glomerulonephritis of C5 or some terminal complement component dependent upon C5 for activation was explored in a congenic strain of C5 sufficient (NSN) and C5 deficient (OSN) mice. When these mice were given daily injections of heterologous protein, horse apoferritin (HAF), there were profound differences between the strains in the development of glomerulonephritis and renal dysfunction. When NSN and OSN mice produced low levels of anti-HAF, NSN mice developed extensive glomerular deposits of HAF and immune reactants and a mild proliferative glomerulonephritis. In contrast, comparable OSN mice developed only trace mesangial localization of HAF and no glomerular lesions by light microscopy. When NSN and OSN mice produced high levels of anti-HAF, both strains had equivalent glomerular immune deposits; however, NSN mice developed a severe necrotizing and crescentic glomerulonephritis, while OSN mice had much less glomerular injury. Compared to OSN mice, these NSN mice also had much more severe tubulointerstitial injury, and significantly higher serum creatinine levels. Thus, in this experimental model, the absence of C5 resulted in reduced glomerular immune complex localization when there were small amounts of circulating immune reactants; and in markedly reduced glomerular leukocyte influx, necrosis and crescent formation, when large amounts of immune reactants have localized in glomeruli. These effects could be mediated by C5 (such as C5a) or by some terminal complement component(s) dependent upon C5 for activation.
D000367:Age Factors; D000818:Animals; D000917:Antibody Formation; D000936:Antigen-Antibody Complex / Q000276:immunology; D000941:Antigens; D001052:Apoferritins / Q000276:immunology; D003182:Complement C5 / Q000172:deficiency*; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000276:immunology*; D006736:Horses / Q000276:immunology; D007105:Immune Complex Diseases / Q000276:immunology*; D007678:Kidney Glomerulus / Q000276:immunology / Q000648:ultrastructure; D008297:Male; D051379:Mice
D000936:Antigen-Antibody Complex; D000941:Antigens; D003182:Complement C5; D001052:Apoferritins