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Intestinal ischemia-reperfusion injury is mediated by the membrane attack complex
W G Austen1, C Kyriakides, J Favuzza
1Department of Surgery and Pathology, Brigham and Women's Hospital, Boston, MA 02215, USA.
Background:
The dependence of intestinal ischemia-reperfusion injury on the classical complement pathway has been shown with the complement antagonist (sCR1) and complement-specific knockout mice. Using C5 deficient mice, we show that the membrane attack complex mediates local injury.
Methods:
Mice underwent intestinal ischemia-reperfusion. Albumin leak and histologic evidence were compared in wildtype mice, wildtypes treated with sCR1, neutrophil-depleted wildtypes, C5-deficient mice, and C5-deficient mice reconstituted with wildtype serum. Neutrophil tissue levels in injured C5-deficient and wildtype intestines were compared.
Results:
C5-deficient mice had a reduction in injury similar to mice treated with sCR1. Injury was restored by reconstitution with wildtype serum. Wildtype injury was unaffected by neutrophil depletion. Injured intestines of C5-deficient and wildtype mice had similar neutrophil levels. Immunohistochemistry of wildtype and reconstituted C5-deficient mice demonstrated injured intestinal epithelium although C5-deficient mice and sCr1-treated mice were similar to sham mice.
Conclusions:
C5-deficient animals are protected from local injury. Injury is unaffected by neutrophil depletion, and the presence of neutrophils in injured tissue is independent of C5. Local injury is C5 dependent, but the action of C5a on granulocytes is not required. Therefore the membrane attack complex mediates local injury.