Apical proteins stimulate complement synthesis by cultured human proximal tubular epithelial cells

There is increasing evidence to suggest that the renal tubular epithelium i s important in the pathogenesis of progressive renal failure resulting from persistent proteinuria. The role of complement in the progression of chron ic renal failure is not well defined, The purpose of this study was to char acterize the production of complement by human proximal tubular epithelial cells exposed to serum proteins at the apical surface, Complement C3 gene e xpression was analyzed by reverse transcription and PCR. C3 protein biosynt hesis was confirmed by metabolic labeling followed by immunoprecipitation a nd quantified by enzyme-linked immunosorbent assay. In the quiescent state, proximal tubular epithelial cells grown on permeable membrane supports sec reted C3 predominantly into the apical medium. The addition of 5 mg/ml seru m proteins led to an 8.9-fold increase in basolateral C3 secretion and a 2. 1-fold increase in apical C3 secretion, altering the ratio of basolateral: apical C3 secretion from 0.44 +/- 0.16 to 1.87 +/- 0.52. C3 mRNA expression was also upregulated in a time- and dose-dependent manner. Serum fractiona tion demonstrated that the stimulant responsible for these effects was in t he molecular weight range 30 to 100 kD. The observed phenomenon was not rep roduced when purified human albumin alone was used as the stimulant. These findings could provide a possible mechanism for the link between proteinuri a and interstitial fibrosis. This may have potential implications for strat egies directed against complement in retarding the progression of chronic r enal failure.