| First Author | Pickering MC | Year | 2006 |
| Journal | Proc Natl Acad Sci U S A | Volume | 103 |
| Issue | 25 | Pages | 9649-54 |
| PubMed ID | 16769899 | Mgi Jnum | J:111031 |
| Mgi Id | MGI:3652641 | Doi | 10.1073/pnas.0601094103 |
| Citation | Pickering MC, et al. (2006) Prevention of C5 activation ameliorates spontaneous and experimental glomerulonephritis in factor H-deficient mice. Proc Natl Acad Sci U S A 103(25):9649-54 |
| abstractText | Membranoproliferative glomerulonephritis (MPGN) type II (dense deposit disease) is an inflammatory renal disease characterized by electron-dense deposits and complement C3 on the glomerular basement membrane. There is no effective therapy. We investigated the role of C5 activation in a model of MPGN that develops spontaneously in complement factor H-deficient mice (Cfh(-/-)). At 12 months there was a significant reduction in mortality, glomerular cellularity, neutrophil numbers, and serum creatinine levels in Cfh(-/-) mice deficient in C5. Excessive glomerular neutrophil numbers, frequently seen in patients with MPGN during disease flares, were also observed in Cfh(-/-) mice after the administration of an antiglomerular basement membrane antibody. This exaggerated injurious phenotype was absent in Cfh(-/-) mice deficient in C5 but not in Cfh(-/-) mice deficient in C6, indicating a key role for C5 activation in the induction of renal lesions. Importantly, the renal injury was completely reversed in Cfh(-/-) mice pretreated with an anti-murine C5 antibody. These results demonstrate an important role for C5 in both spontaneous MPGN and experimentally induced nephritis in factor H-deficient mice and provide preliminary evidence that C5 inhibition therapy might be useful in human MPGN type II. |
