THE ROLE OF COMPLEMENT IN THE PATHOGENESIS OF TUBULOINTERSTITIAL LESIONS IN RAT MESANGIAL PROLIFERATIVE GLOMERULONEPHRITIS

Persistent proteinuria and tubulointerstitial lesions are important si gns of progressive renal disease. The purpose of this study was to ass ess the role of complement in the development of tubulointerstitial le sions in rats with proteinuria due to primary glomerulonephritis. Mesa ngial proliferative glomerulonephritis was induced in mononephrectomiz ed rats by intravenous injection of monoclonal antibody (mAb) 1-22-3 ( Clin Exp Immunol 102: 181-185, 1995). As early as 24 h after the injec tion, proteinuria became evident, persisted throughout the observation period, and was associated with mesangial cell proliferation and tubu lointerstitial lesions when examined at 7 and 14 d after mAb administr ation. Deposition of rat C3 and C5b-9 was observed at the luminal surf ace of proximal tubules and in cellular debris present in the tubular lumen (group I). Rats injected with mAb 1-22-3 and depleted of complem ent by injections of cobra venom factor starting at day 3 developed gl omerulonephritis and proteinuria comparable to rats of group I, but co mplement deposition in the tubules and the tubulointerstitial lesions were markedly reduced (group II). Rats in group IU were injected with mAb and, from day 3, with soluble complement receptor type 1, which be came detectable at the luminal surface of proximal tubules and in the urine. Deposition of C5b-9 in tubular cells was not detectable, and th e severity of tubulointerstitial lesions was reduced compared with rat s in group I. These results indicate that, in this model of primary me sangial proliferative glomerulonephritis with proteinuria, the develop ment of tubulointerstitial lesions is associated with activation of se rum complement at the level of tubular brush border, and tubulointerst itial lesions can be reduced by inhibition of complement activity.