The role of complement in the pathogenesis of tubulointerstitial lesions in rat mesangial proliferative glomerulonephritis

Yoshiki Morita, Atsushi Nomura, Yukio Yuzawa, Kazuhiro Nishikawa, Nigishi Hotta, Fujio Shimizu, Seiichi Matsuo

研究成果: Article査読

64 被引用数 (Scopus)

抄録

Persistent proteinuria and tubulointerstitial lesions are important signs of progressive renal disease. The purpose of this study was to assess the role of complement in the development of tubulointerstitial lesions in rats with proteinuria due to primary glomerulonephritis. Mesangial proliferative glomerulonephritis was induced in mononephrectomized 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 injection, proteinuria became evident, persisted throughout the observation period, and was associated with mesangial cell proliferation and tubulointerstitial lesions when examined at 7 and 14 d after mAb administration. Deposition of rat C3 and C5b-9 was observed at the luminal surface of proximal tubules and in cellular debris present in the tubular lumen (group I). Rats injected with mAb 1-22-3 and depleted of complement by injections of cobra venom factor starting at day 3 developed glomerulonephritis and proteinuria comparable to rats of group I, but complement deposition in the tubules and the tubulointerstitial lesions were markedly reduced (group II). Rats in group III were injected with mAb and, from day 3, with soluble complement receptor type 1, which became detectable at the luminal surface of proximal tubules and in the urine. Deposition of C5b-9 in tubular cells was not detectable, and the severity of tubulointerstitial lesions was reduced compared with rats in group I. These results indicate that, in this model of primary mesangial proliferative glomerulonephritis with proteinuria, the development of tubulointerstitial lesions is associated with activation of serum complement at the level of tubular brush border, and tubulointerstitial lesions can be reduced by inhibition of complement activity.

本文言語English
ページ(範囲)1363-1372
ページ数10
ジャーナルJournal of the American Society of Nephrology
8
9
出版ステータスPublished - 09-1997
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腎臓病学

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