[Role of complement in experimental glomerulonephritis].

The complement system is composed by 26 plasmatic proteins. The activation of either the classical or alternative complement pathway leads to the formation of the membrane attack complex C5b-C9 (MAC) which is capable of producing damage of the cellular membrane. MAC has been identified in renal biopsies from human and experimental, immune and nonimmune renal diseases, but it has not been possible to demonstrate any enzymatic activity on the glomerular basement membrane components (GBM). MAC can produce a lytic or a nonlytic effect on renal cells depending upon the dose used. The lytic effect in vitro has been demonstrated in epithelial, mesangial and endothelial cells, whereas the lytic effect in vivo has been described in a model of acute glomerulonephritis produced by the administration of monoclonal antibody anti-Thy 1.1. which reacts with mesangial cells. The nonlytic effect of MAC on renal cells is characterized by alterations in cell metabolism which can lead the production of prostaglandins, type IV collagen, reactive oxygen species, and a growth factor resembling interleukin I which can contribute to glomerular damage, to the modification of the filtration barrier permeability and hemodynamic changes in experimental glomerulonephritis. The effector mechanisms by which the complement system participates in the pathogenesis of glomerulonephritis are different in the various experimental models of nephritis. In nephrotoxic nephritis the complement pathway participates at least in 3 different ways: a) complement-neutrophil mediated injury, b) MAC dependent mechanism and c) producing hemodynamic alterations. In acute serum sickness the complement system beyond C2 is not necessary for the development of proteinuria and glomerular inflammation, but the MAC assembly seems to be important for the formation of large deposits. In the chronic serum sickness model, the complement system participates in the early proteinuria as well as in the histological expression of the disease. In the heterologous phase of Heymann's nephritis, the proteinuria is complement dependent whereas in the autologous phase the damage depends upon cellular mediated immunity. In passive Heymann's nephritis the complement system and particularly MAC, has a central role for the histological lesion of the epithelial cell as well as in the proteinuria. In conclusion, the complement system can mediate renal damage by the following mechanism: a) Releasing chemotactic factors which result in neutrophil recruitment and neutrophil mediated glomerular damage.(ABSTRACT TRUNCATED AT 400 WORDS)