Blockade of L-selectin attenuates reperfusion injury in a rat model.
Ischemia/reperfusion (I/R) injury appears to be a significant neutrophil-dependent component and may be ameliorated by blocking leukocyte-endothelial adhesion. Using a rat extensor digitorum longus (EDL) muscle model, the present study tested the hypothesis that in vivo administration of the function-blocking monoclonal antibody (mAb) LAM1-116 which recognizes L-selectin, a cell-surface adhesion receptor, could decrease I/R injury. In 46 rats, one EDL served as a normal control and the opposite EDL underwent 3 hr of ischemia followed by 3 hr of reperfusion after pretreatment with LAM1-116 mAb, control IgG, or saline. Myeloperoxidase (MPO) activity showed only a two-fold increase from normal in LAM1-116-treated I/R EDL while a 27-fold increase occurred in the IgG2a and saline groups, with a statistically significant (p < 0.001) difference. A significantly (p < 0.05) lower wet weight ratio, improved fatigue contractile force, and less neutrophil infiltration were found in LAM1-116-treated EDL, when compared to those in control IgG- or saline-treated EDL. The results indicate that blockade of L-selectin by LAM1-116 mAb can effectively reduce neutrophil infiltration in reperfused skeletal muscle, thereby decreasing tissue edema and improving muscle fatigue contractile force. These findings may be important in understanding I/R injury.
Yan
Z Q
ZQ
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Bolognesi
M P
MP
Steeber
D A
DA
Tedder
T F
TF
Chen
L E
LE
Seaber
A V
AV
Urbaniak
J R
JR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007074:Immunoglobulin G / Q000378:metabolism / Q000494:pharmacology; D019041:L-Selectin / Q000187:drug effects* / Q000378:metabolism; D007958:Leukocyte Count / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D012680:Sensitivity and Specificity
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D019041:L-Selectin; D009195:Peroxidase