INTRAGLOMERULAR C3 SYNTHESIS IN RATS WITH PASSIVE HEYMANN NEPHRITIS

Passive Heymann nephritis (PHN), a model of human membranous nephropat hy, is an immune-complex-mediated glomerulonephritis characterized by the presence of complement-dependent tissue injury. Recent studies hav e confirmed the synthesis of C3, involved in both the classical and al ternative pathways of complement, in injured human and animal renal ti ssues. However, there is little clear information on the role of local C3 synthesis in the pathogenesis of nephritides such as PHN. In the p resent study, using nonradioactive in situ hybridization and semiquant itative reverse transcriptase polymerase chain reaction, we examined C 3 synthesis in the kidney and its contribution to tissue injury in a r at model of PHN induced by the injection of polyclonal anti-gp330 anti body. C3 mRNA was localized in mesangial cells, glomerular epithelial cells, and cells of Bowman's capsule. During the early stages of PHN, C3 mRNA expression was detected in mesangial cells and glomerular epit helial cells, whereas such expression was limited to mesangial cells d uring the late stages of the disease. Focal, weak C3 mRNA expression w as detected in tubular epithelial cells and occasionally in the inters titium. Semiquantitative polymerase chain reaction demonstrated that t he level of C3 mRNA expression correlated with that of proteinuria. Ou r results suggest that renal cells synthesize C3 mRNA in PHN in a site -specific manner and that locally produced C3 is associated with the d evelopment of proteinuria in this model.