Reperfusion injury of ischemic skeletal muscle is mediated by natural antibody and complement

J Exp Med. 1996 May 1;183(5):2343-8. doi: 10.1084/jem.183.5.2343.


Reperfusion of ischemic tissue induces an acute inflammatory response that can result in necrosis and irreversible cell injury to both local vascular endothelium and parenchyma. To examine the pathogenesis of ischemia/reperfusion injury, we have used mice deficient in complement components C3, C4, or serum immunoglobulin in a hindlimb model of ischemia. We found that mice homozygous deficient in C3 or C4 were equally protected against reperfusion injury based on a significant reduction in leakage of radiolabeled albumin out of the vasculature. This demonstrates that classical pathway complement is an important factor in the initiation of inflammation following reperfusion. Furthermore, mice deficient in serum immunoglobulin were equally protected and this protection could be reversed by reconstitution with serum from normal mice. Thus, this report describes a novel mechanism for reperfusion injury that involves antibody deposition and activation of complement leading to inflammation permeability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Complement C3 / deficiency
  • Complement C4 / deficiency
  • Complement Pathway, Classical
  • Complement System Proteins / deficiency
  • Complement System Proteins / physiology*
  • Immunoglobulin M / analysis
  • Immunoglobulins / deficiency*
  • Ischemia / immunology*
  • Ischemia / pathology
  • Mice
  • Mice, Mutant Strains
  • Muscle, Skeletal / blood supply*
  • Muscle, Skeletal / pathology
  • Reperfusion Injury / immunology*
  • Reperfusion Injury / pathology


  • Complement C3
  • Complement C4
  • Immunoglobulin M
  • Immunoglobulins
  • Complement System Proteins