Respective roles of decay-accelerating factor and CD59 in circumventing glomerular injury in acute nephrotoxic serum nephritis.

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 microg/mg creatinine in the WT controls (p > 0.1). After NTS, albuminuria in CD59a(-/-) and WT mice (186 +/- 154 and 183 +/- 137 microg/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 micro g/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.

• Authors: Feng Lin, David J Salant, Howard Meyerson, Steven Emancipator, B Paul Morgan, M Edward Medof
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 172 Issue 4 Pg. 2636-42 (Feb 15 2004) ISSN: 0022-1767 [Print] United States
• PMID: 14764738 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CD55 Antigens
• CD59 Antigens
• Complement C3
• Complement C9
• Immune Sera

Topics

• Acute Disease
• Animals
• Autoimmune Diseases (genetics, immunology, pathology)
• CD55 Antigens (genetics, physiology)
• CD59 Antigens (genetics, physiology)
• Complement C3 (metabolism)
• Complement C9 (metabolism)
• Complement Pathway, Classical (genetics)
• Fluorescent Antibody Technique
• Glomerulonephritis (genetics, immunology, pathology)
• Immune Sera (toxicity)
• Kidney Glomerulus (immunology, pathology, ultrastructure)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Proteinuria (genetics, immunology, pathology)