Skeletal muscle reperfusion injury is mediated by neutrophils and the complement membrane attack complex.
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.
Kyriakides
C
C
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Austen
W
W
Wang
Y
Y
Favuzza
J
J
Kobzik
L
L
Moore
F D
FD
Hechtman
H B
HB
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
D000906:Antibodies; D003176:Complement C3; D003182:Complement C5; D015938:Complement Membrane Attack Complex; D007075:Immunoglobulin M; D019087:Selectins