Critical Protection from Renal Ischemia Reperfusion Injury by CD55 and CD59

Koei Yamada, Takashi Miwa, Jianuo Liu, Masaomi Nangaku, Wen Chao Song

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Renal ischemia-reperfusion injury (IRI) is a feature of ischemic acute renal failure and it impacts both short- and long-term graft survival after kidney transplantation. Complement activation has been implicated in renal IRI, but its mechanism of action is uncertain and the determinants of complement activation during IRI remain poorly understood. We engineered mice deficient in two membrane complement regulatory proteins, CD55 and CD59, and used them to investigate the role of these endogenous complement inhibitors in renal IRI. CD55-deficient (CD55-/-), but not CD59-deficient (CD59 -/-), mice exhibited increased renal IRI as indicated by significantly elevated blood urea nitrogen levels, histological scores, and neutrophil infiltration. Remarkably, although CD59 deficiency alone was inconsequential, CD55/CD59 double deficiency greatly exacerbated IRI. Severe IRI in CD55-/-CD59-/- mice was accompanied by endothelial deposition of C3 and the membrane attack complex (MAC) and medullary capillary thrombosis. Complement depletion in CD55-/-CD59-/- mice with cobra venom factor prevented these effects. Thus, CD55 and CD59 act synergistically to inhibit complement-mediated renal IRI, and abrogation of their function leads to MAC-induced microvascular injury and dysfunction that may exacerbate the initial ischemic assault. Our findings suggest a rationale for anti-complement therapies aimed at preventing microvascular injury during ischemia reperfusion, and the CD55-/-CD59-/- mouse provides a useful animal model in this regard.

Original languageEnglish (US)
Pages (from-to)3869-3875
Number of pages7
JournalJournal of Immunology
Volume172
Issue number6
DOIs
StatePublished - Mar 15 2004

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Reperfusion Injury
Kidney
Complement Membrane Attack Complex
Complement Activation
Complement Inactivating Agents
Neutrophil Infiltration
Blood Urea Nitrogen
Graft Survival
Acute Kidney Injury
Kidney Transplantation
Complement System Proteins
Membrane Proteins
Thrombosis
Animal Models
Wounds and Injuries

ASJC Scopus subject areas

  • Immunology

Cite this

Critical Protection from Renal Ischemia Reperfusion Injury by CD55 and CD59. / Yamada, Koei; Miwa, Takashi; Liu, Jianuo; Nangaku, Masaomi; Song, Wen Chao.

In: Journal of Immunology, Vol. 172, No. 6, 15.03.2004, p. 3869-3875.

Research output: Contribution to journalArticle

Yamada, K, Miwa, T, Liu, J, Nangaku, M & Song, WC 2004, 'Critical Protection from Renal Ischemia Reperfusion Injury by CD55 and CD59', Journal of Immunology, vol. 172, no. 6, pp. 3869-3875. https://doi.org/10.4049/jimmunol.172.6.3869
Yamada, Koei ; Miwa, Takashi ; Liu, Jianuo ; Nangaku, Masaomi ; Song, Wen Chao. / Critical Protection from Renal Ischemia Reperfusion Injury by CD55 and CD59. In: Journal of Immunology. 2004 ; Vol. 172, No. 6. pp. 3869-3875.
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