Evidence for increased synthesis of complement C4 in the renal epithelium of rats with passive Heymann nephritis

Passive Heymann nephritis (PHN) is a complement-dependent model of immune complex glomerulonephritis. This study investigated the contribution of local complement synthesis by studying gene expression of the classical pathway component C4 in relation to the site of the tissue injury and the development of proteinuria induced by the pathogenic antibody (sheep anti-GP330). This study, using in situ hybridization, found that C4 mRNA expression was increased in the glomerular epithelium and the proximal renal tubular epithelium in a distribution similar to that of the targeted GP330 antigen. The total cortical C4 mRNA expression assessed by semiquantitative polymerase chain reaction (PCR) increased in a time-dependent manner (P < 0.05), coincident with the onset and progression of proteinuria, and peaking 11 to 14 days after the induction of the disease. These data suggest a link, in place and time, between local complement gene expression and glomerular barrier dysfunction induced by anti-GP330. It is postulated that increased epithelial synthesis of C4 stimulated by the engagement of GP330 enhances the formation of the membrane attack complex of complement through its classical pathway, and, hence, the formation of complement-mediated injury.