Increased susceptibility of decay-accelerating factor deficient mice to anti-glomerular basement membrane glomerulonephritis

H. Sogabe, M. Nangaku, Y. Ishibashi, T. Wada, T. Fujita, X. Sun, T. Miwa, M. P. Madaio, W. C. Song

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

To prevent complement-mediated autologous tissue damage, host cells express a number of membrane-bound complement inhibitors. Decay-accelerating factor (DAF, CD55) is a GPI-linked membrane complement regulator that is widely expressed in mammalian tissues including the kidney. DAF inhibits the C3 convertase of both the classical and alternative pathways. Although DAF deficiency contributes to the human hematological syndrome paroxysmal nocturnal hemoglobinuria, the relevance of DAF in autoimmune tissue damage such as immune glomerulonephritis remains to be determined. In this study, we have investigated the susceptibility of knockout mice that are deficient in GPI-anchored DAF to nephrotoxic serum nephritis. Injection of a subnephritogenic dose of rabbit anti-mouse glomerular basement membrane serum induced glomerular disease in DAF knockout mice but not in wild-type controls. When examined at 8 days after anti-glomerular basement membrane treatment, DAF knockout mice had a much higher percentage of diseased glomeruli than wild-type mice (68.8 ± 25.0 vs 10.0 ± 3.5%; p < 0.01). Morphologically, DAF knockout mice displayed increased glomerular volume (516 ± 68 vs 325 ± 18 × 103 μm3 per glomerulus; p < 0.0001) and cellularity (47.1 ± 8.9 vs 32.0 ± 3.1 cells per glomerulus; p < 0.01). Although the blood urea nitrogen level showed no difference between the two groups, proteinuria was observed in the knockout mice but not in the wild-type mice (1.4 ± 0.7 vs 0.02 ± 0.01 mg/24 h albumin excretion). The morphological and functional abnormalities in the knockout mouse kidney were associated with evidence of increased complement activation in the glomeruli. These results support the conclusion that membrane C3 convertase inhibitors like DAF play a protective role in complement-mediated immune glomerular damage in vivo.

Original languageEnglish (US)
Pages (from-to)2791-2797
Number of pages7
JournalJournal of Immunology
Volume167
Issue number5
DOIs
StatePublished - Sep 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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