title: Skeletal muscle reperfusion injury is mediated by neutrophils and the complement membrane attack complex.
abstract: 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.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: C
authors.initials: C
authors.lastname: Kyriakides
authors.forename: W
authors.initials: W
authors.lastname: Austen
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Favuzza
authors.forename: L
authors.initials: L
authors.lastname: Kobzik
authors.forename: F D
authors.initials: FD
authors.lastname: Moore
authors.forename: H B
authors.initials: HB
authors.lastname: Hechtman
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000276:immunology; D003176:Complement C3 / Q000032:analysis; D003182:Complement C5 / Q000235:genetics; D015938:Complement Membrane Attack Complex / Q000032:analysis / Q000276:immunology*; D006614:Hindlimb; D007075:Immunoglobulin M / Q000032:analysis; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000276:immunology* / Q000473:pathology; D009504:Neutrophils / Q000276:immunology*; D015427:Reperfusion Injury / Q000276:immunology*; D019087:Selectins / Q000276:immunology
chemical_list: D000906:Antibodies; D003176:Complement C3; D003182:Complement C5; D015938:Complement Membrane Attack Complex; D007075:Immunoglobulin M; D019087:Selectins