Complement component C3 is not required for full expression of immune complex glomerulonephritis in MRL/lpr mice

Hideharu Sekine, Christopher M. Reilly, Ivan D. Molano, Gérard Garnier, Antonella Circolo, Philip Ruiz, V. Michael Holers, Susan A. Boackle, Gary S. Gilkeson

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108 Scopus citations

Abstract

Complement activation and tissue deposition of complement fragments occur during disease progression in lupus nephritis. Genetic deficiency of some complement components (e.g., Factor B) and infusion of complement inhibitors (e.g., Crry, anti-C5 Ab) protect against inflammatory renal disease. Paradoxically, genetic deficiencies of early components of the classical complement pathway (e.g., C1q, C4, and C2) are associated with an increased incidence of lupus in humans and lupus-like disease in murine knockout strains. Complement protein C3 is the converging point for activation of all three complement pathways and thus plays a critical role in biologic processes mediated by complement activation. To define the role of C3 in lupus nephritis, mice rendered C3 deficient by targeted deletion were backcrossed for eight generations to MRL/lpr mice, a mouse strain that spontaneously develops lupus-like disease. We derived homozygous knockout (C3-/-), heterozygous (C3+/-), and C3 wild-type (C3+/+) MRL/lpr mice. Serum levels of autoantibodies and circulating immune complexes were similar among the three groups. However, there was earlier and significantly greater albuminuria in the C3-/- mice compared with the other two groups. Giomerular IgG deposition was also significantly greater in the C3-/- mice than in the other two groups, although overall pathologic renal scores were similar. These results indicate that C3 and/or activation of C3 is not required for full expression of immune complex renal disease in MRL/lpr mice and may in fact play a beneficial role via clearance of immune complexes.

Original languageEnglish (US)
Pages (from-to)6444-6451
Number of pages8
JournalJournal of Immunology
Volume166
Issue number10
DOIs
StatePublished - May 15 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sekine, H., Reilly, C. M., Molano, I. D., Garnier, G., Circolo, A., Ruiz, P., Holers, V. M., Boackle, S. A., & Gilkeson, G. S. (2001). Complement component C3 is not required for full expression of immune complex glomerulonephritis in MRL/lpr mice. Journal of Immunology, 166(10), 6444-6451. https://doi.org/10.4049/jimmunol.166.10.6444