Tubulointerstitial injury induced in rats by a monoclonal antibody that inhibits function of a membrane inhibitor of complement

Atsushi Nomura, Kazuhiro Nishikawa, Yukio Yuzawa, Hidechika Okada, Noriko Okada, B. Paul Morgan, Sara J. Piddlesden, Masayuki Nadai, Takaaki Hasegawa, Seiichi Matsuo

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Abstract

The kidney widely expresses membrane-associated complement regulatory proteins (membrane inhibitors of complement). The aim of this work was to evaluate the roles of these molecules in rat kidneys in vivo. To suppress functions of rat membrane inhibitors of complement, two mAbs, 512 and 6D1, were used. 512 and 6D1 inhibit functions of membrane inhibitors of complement at C3 level (rat Crry/p65) and C8/9 level (rat CD59), respectively. F(ab')2 fragment of 512 or 6D1 was perfused in the left kidneys, and perfusate was discarded from the renal vein. After perfusion, the left kidneys were connected to systemic circulation. In rats perfused with 512, mouse IgG was found in glomeruli, peritubular capillaries, vascular bundles, and tubules 15 min after recirculation. Binding of C3 and C5b-9 was evident in these areas. 1 d after perfusion with 512, cast formation, dilatation of tubular lumen, and tubular cell degeneration were observed. At day 4 through day 7, significant mononuclear cell infiltration and proximal tubule damage were observed. These changes were completely prevented by complement depletion. Rats perfused with 6D1 showed the binding of mouse IgG in the similar areas as 512, but C3 or C5b-9 deposition was nut observed. Rats perfused with 6D1 or vehicle only did not show any pathology in the left kidneys. These results suggest that rat Crry/p65 plays protective roles against spontaneously occurring indiscriminate attack to tubulointerstitial tissues by autologous complement and that rat Crry/p65 is one of the important factors to maintain normal integrity of the kidney in rats.

Original languageEnglish
Pages (from-to)2348-2356
Number of pages9
JournalJournal of Clinical Investigation
Volume96
Issue number5
DOIs
Publication statusPublished - 11-1995

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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    Nomura, A., Nishikawa, K., Yuzawa, Y., Okada, H., Okada, N., Morgan, B. P., Piddlesden, S. J., Nadai, M., Hasegawa, T., & Matsuo, S. (1995). Tubulointerstitial injury induced in rats by a monoclonal antibody that inhibits function of a membrane inhibitor of complement. Journal of Clinical Investigation, 96(5), 2348-2356. https://doi.org/10.1172/JCI118291