Respective Roles of Decay-Accelerating Factor and CD59 in Circumventing Glomerular Injury in Acute Nephrotoxic Serum Nephritis

  • Lin F
  • Salant D
  • Meyerson H
  • et al.
35Citations
Citations of this article
15Readers
Mendeley users who have this article in their library.

Abstract

Decay-accelerating factor (DAF or CD55) and CD59 are regulators that protect self cells from C3b deposition and C5b-9 assembly on their surfaces. Their relative roles in protecting glomeruli in immune-mediated renal diseases in vivo are unknown. We induced nephrotoxic serum (NTS) nephritis in Daf1−/−, CD59a−/−, Daf1−/−CD59a−/−, and wild-type (WT) mice by administering NTS IgG. After 18 h, we assessed proteinuria, and performed histological, immunohistochemical, and electron microscopic analyses of kidneys. Twenty-four mice in each group were studied. Baseline albuminuria in the Daf1−/−, CD59a−/−, and Daf1−/−CD59a−/− mice was 82, 83, and 139 as compared with 92 μg/mg creatinine in the WT controls (p > 0.1). After NTS, albuminuria in CD59a−/− and WT mice (186 ± 154 and 183 ± 137 μg/mg creatinine, p > 0.1) was similar. In contrast, Daf1−/− mice developed severe albuminuria (378 ± 520, p < 0.05) that was further exacerbated in Daf1−/−CD59a−/− mice (577 ± 785 μg/mg creatinine, p < 0.05). Glomerular histology showed essentially no infiltrating leukocytes in any group. In contrast, electron microscopy revealed prominent podocyte foot process effacement in Daf1−/− mice with more widespread and severe damage in the double knockouts compared with only mild focal changes in CD59a−/− or WT mice. In all animals, deposition of administered (sheep) NTS Ig was equivalent. This contrasted with marked deposition of both C3 and C9 in Daf1−/−CD59a−/− and Daf1−/− mice, which was evident as early as 2 h post-NTS injection. The results support the proposition that in autoantibody-mediated nephritis, DAF serves as the primary barrier to classical pathway-mediated injury, while CD59 limits consequent C5b-9-mediated cell damage.

Cite

CITATION STYLE

APA

Lin, F., Salant, D. J., Meyerson, H., Emancipator, S., Morgan, B. P., & Medof, M. E. (2004). Respective Roles of Decay-Accelerating Factor and CD59 in Circumventing Glomerular Injury in Acute Nephrotoxic Serum Nephritis. The Journal of Immunology, 172(4), 2636–2642. https://doi.org/10.4049/jimmunol.172.4.2636

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free