Skeletal muscle reperfusion injury is mediated by neutrophils and the complement membrane attack complex

Am J Physiol. 1999 Dec;277(6):C1263-8. doi: 10.1152/ajpcell.1999.277.6.C1263.


The relative inflammatory roles of neutrophils, selectins, and terminal complement components are investigated in this study of skeletal muscle reperfusion injury. Mice underwent 2 h of hindlimb ischemia followed by 3 h of reperfusion. The role of neutrophils was defined by immunodepletion, which reduced injury by 38%, as did anti-selectin therapy with recombinant soluble P-selectin glycoprotein ligand-immunoglobulin (Ig) fusion protein. Injury in C5-deficient and soluble complement receptor type 1-treated wild-type mice was 48% less than that of untreated wild-type animals. Injury was restored in C5-deficient mice reconstituted with wild-type serum, indicating the effector role of C5-9. Neutropenic C5-deficient animals showed additive reduction in injuries (71%), which was lower than C5-deficient neutrophil-replete mice, indicating neutrophil activity without C5a. Hindlimb histological injury was worse in ischemic wild-type and C5-deficient animals reconstituted with wild-type serum. In conclusion, the membrane attack complex and neutrophils act additively to mediate skeletal muscle reperfusion injury. Neutrophil activity is independent of C5a but is dependent on selectin-mediated adhesion.

Publication types

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

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Cell Membrane Permeability / immunology
  • Complement C3 / analysis
  • Complement C5 / genetics
  • Complement Membrane Attack Complex / analysis
  • Complement Membrane Attack Complex / immunology*
  • Hindlimb
  • Immunoglobulin M / analysis
  • Male
  • Mice
  • Mice, Mutant Strains
  • Muscle, Skeletal / blood supply*
  • Muscle, Skeletal / immunology*
  • Muscle, Skeletal / pathology
  • Neutrophils / immunology*
  • Reperfusion Injury / immunology*
  • Selectins / immunology


  • Antibodies
  • Complement C3
  • Complement C5
  • Complement Membrane Attack Complex
  • Immunoglobulin M
  • Selectins