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

The relative inflammatory roles of neutrophils, selectins, and terminal com plement components are investigated in this study of skeletal muscle reperf usion injury. Mice underwent 2 h of hindlimb ischemia followed by 3 h of re perfusion. The role of neutrophils was de fined by immunodepletion, which r educed 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 I-treated wild-type mi ce was 48% less than that of untreated wild-type animals. Injury was restor ed in CS-deficient mice reconstituted with wild-type serum, indicating the effector role of C5-9. Neutropenic C5-deficient animals showed additive red uction in injuries (71%), which was lower than C5-deficient neutrophil-repl ete mice, indicating neutrophil activity without C5a. Hindlimb histological injury was worse in ischemic wild-type and C5-deficient animals reconstitu ted with wild-type serum. In conclusion, the membrane attack complex and ne utrophils act additively to mediate skeletal muscle reperfusion injury. Neu trophil activity is independent of C5a but is dependent on selectin-mediate d adhesion.