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

The relative inflammatory roles ofneutrophils, selectins, and terminal complement components areinvestigated in this study of skeletal muscle reperfusion injury. Miceunderwent 2 h of hindlimb ischemia followed by 3 h ofreperfusion. The role of neutrophils was defined by immunodepletion,which reduced injury by 38%, as did anti-selectin therapy withrecombinant soluble P-selectin glycoprotein ligand-immunoglobulin (Ig)fusion protein. Injury in C5-deficient and soluble complement receptortype 1-treated wild-type mice was 48% less than that of untreatedwild-type animals. Injury was restored in C5-deficient micereconstituted with wild-type serum, indicating the effector role ofC5-9. Neutropenic C5-deficient animals showed additive reductionin injuries (71%), which was lower than C5-deficientneutrophil-replete mice, indicating neutrophil activity withoutC5a. Hindlimb histological injury was worse in ischemicwild-type and C5-deficient animals reconstituted with wild-type serum.In conclusion, the membrane attack complex and neutrophils actadditively to mediate skeletal muscle reperfusion injury. Neutrophilactivity is independent of C5a but is dependent on selectin-mediated adhesion.