Role of neutrophil-endothelial adhesion in skeletal muscle reperfusion injury.
During postischaemic revascularization neutrophil-endothelial adhesion in the skeletal muscle microcirculation, promoted by the neutrophil adhesion molecule Mac-1, may impair muscle blood flow and release oxygen free radicals and proteolytic enzymes which causes further tissue injury. This study has assessed the effect of an anti-Mac-1 monoclonal antibody on the severity of skeletal muscle injury in a rat model of 6-h hindlimb ischaemia and 4-h reperfusion. In control animals a sustained impairment of muscle perfusion was associated with neutrophil sequestration, muscle infarction and muscle oedema (P < 0.001 versus normal rats). In contrast, intravenous administration of anti-Mac-1 monoclonal antibody before revascularization prevented neutrophil recruitment, reduced muscle necrosis and improved postischaemic muscle perfusion at 120 and 240 min (not significantly different from normal), thus confirming that neutrophils are important cellular mediators of skeletal muscle reperfusion injury. Monoclonal antibodies targeting neutrophil adhesion molecules may, therefore, have a role in the prevention of this complication of limb revascularization.
Crinnion
J N
JN
Vascular Surgical Unit, Leeds General Infirmary, UK.
Homer-Vanniasinkam
S
S
Parkin
S M
SM
Gough
M J
MJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D004487:Edema; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D018482:Muscle, Skeletal / Q000098:blood supply*; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology* / Q000628:therapy
D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen; D009195:Peroxidase