Membrane attack complex contributes to destruction of vascular integrity in acute lung allograft rejection

Shinji Nakashima, Zhiping Qian, Salma Rahimi, Barbara A. Wasowska, William M. Baldwin

Research output: Contribution to journalArticlepeer-review

Abstract

The lung is known to be particularly susceptible to complement-mediated injury. Both C5a and the membrane attack complex (MAC), which is formed by the terminal components of complement (C5b-C9), can cause acute pulmonary distress in nontransplanted lungs. We used C6-deficient rats to investigate whether MAC causes injury to lung allografts. PVG.R8 lungs were transplanted orthotopically to MHC class I-incompatible PVG.1U recipients. Allografts from C6-sufficient (C6+) donors to C6+ recipients were rejected with an intense vascular infiltration and diffuse alveolar hemorrhage 7 days after transplantation (n = 5). Ab and complement (C3d) deposition was accompanied by extensive vascular endothelial injury and intravascular release of von Willebrand factor. In contrast, lung allografts from C6-deficient (C6-) donors to C6- recipients survived 13-17 days (n = 5). In the absence of C6, perivascular mononuclear infiltrates of ED1+ macrophages and CD8+ T lymphocytes were present 7 days after transplantation, but vascular endothelial cells were quiescent, with minimal von Willebrand factor release and no evidence of alveolar hemorrhage or edema. Lung allografts were performed from C6- donors to C6+ recipients (n = 5) and from C6+ donors to C6- recipients (n = 5) to separate the effects of systemic and local C6 production. Lungs transplanted from C6+ donors to C6- recipients had increased alveolar macrophages and capillary injury. C6 production by lung allografts was demonstrated at the mRNA and protein levels. These results demonstrate that MAC causes vascular injury in lung allografts and that the location of injury is dependent on the source of C6.

Original languageEnglish (US)
Pages (from-to)4620-4627
Number of pages8
JournalJournal of Immunology
Volume169
Issue number8
StatePublished - Oct 15 2002

ASJC Scopus subject areas

  • Immunology

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