Role of a rat membrane inhibitor of complement in anti-basement membrane antibody-induced renal injury

Yuji Hatanaka, Yukio Yuzawa, Kazuhiro Nishikawa, Atsushi Fukatsu, Noriko Okada, Hidechika Okada, Masashi Mizuno, Seiichi Matsuo

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Abstract

In the kidneys of anti-glomerular basement membrane (anti-GBM) antibody disease, binding of antibodies to tubular basement membrane (TBM) is often observed. The present work was performed to explore the mechanisms of binding of anti-GBM antibodies to TBM in vivo with special reference to 5I2Ag, a rat membrane inhibitor of complement which regulates complement activation at C3 convertase level. To suppress functions of renal 512Ag, F(ab')2 fragment of 512 (a neutralizing mAb against 512Ag) was perfused in the left kidney and then blood circulation was restored. Mild proteinuria (< 10 mg/16 hr) was observed during first several days. Five days later, there were tubulointerstitial injuries defined by tubular vimentin staining and leukocyte infiltration. Significant deposition of C3 was observed in the capillaries and in TBM. In rats intravenously injected with rabbit anti-rat GBM antibodies five minutes after kidney perfusion with 512, strong binding of rabbit IgG to TBM was observed at one and five days after injection. Although these rats showed mild proteinuria comparable to those perfused with 512 and those injected with normal rabbit serum, tubulointerstitial injury was significantly enhanced at Day 5. In contrast, rats perfused with irrelevant mAb and injected with anti-GBM antibodies did not show any significant binding of antibodies to TBM nor tubulointerstitial injury. Furthermore, rats which were made proteinuric by puromycin aminonucleoside and injected with anti-GBM antibodies did not show any significant binding of rabbit IgG to TBM. These results indicate that 512Ag, a rat membrane inhibitor of complement at the C3 convertase level, regulates vascular permeability in the living kidney, and that dysfunction or decreased expression of this molecule leads to increased accessibility of anti-GBM antibodies to TBM.

Original languageEnglish
Pages (from-to)1728-1737
Number of pages10
JournalKidney International
Volume48
Issue number6
DOIs
Publication statusPublished - 12-1995

All Science Journal Classification (ASJC) codes

  • Nephrology

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    Hatanaka, Y., Yuzawa, Y., Nishikawa, K., Fukatsu, A., Okada, N., Okada, H., Mizuno, M., & Matsuo, S. (1995). Role of a rat membrane inhibitor of complement in anti-basement membrane antibody-induced renal injury. Kidney International, 48(6), 1728-1737. https://doi.org/10.1038/ki.1995.471