Circulation, Vol 88, 649-658, Copyright © 1993 by American Heart Association
XL Ma, AS Weyrich, DJ Lefer, M Buerke, KH Albertine, TK Kishimoto and AM Lefer
BACKGROUND. Interaction of CD11/CD18 located on neutrophil membranes with
its endothelial counter-receptor, intercellular adhesion molecule- 1, plays
a major role in polymorphonuclear leukocyte (PMN)-mediated endothelial
dysfunction and myocardial injury associated with ischemia and reperfusion.
However, PMN-derived L-selectin, which is thought to play an early role in
PMN rolling along the vascular endothelium, has not been studied in a
setting of myocardial ischemia and reperfusion. METHODS AND RESULTS. In
this study, we evaluated the effects of a monoclonal antibody against
L-selectin, DREG-200, in a feline model of myocardial ischemia (1.5 hours)
and reperfusion (4.5 hours). DREG-200 (1 mg/kg) or an isotype-matched IgG1
antibody, MAb R3.1, which does not cross-react in cats, was administered as
a bolus 10 minutes before reperfusion. In MAb R3.1-treated cats, myocardial
ischemia followed by reperfusion resulted in significant coronary vascular
endothelial dysfunction, elevated cardiac myeloperoxidase activity
indicative of neutrophil accumulation in the ischemic myocardium, and
severe myocardial injury. In contrast, administration of DREG-200 at 1
mg/kg significantly attenuated myocardial necrosis (14 +/- 4 versus 32 +/-
3 expressed as percentage of area at risk, P < .001) and attenuated
coronary endothelial dysfunction (P < .01) associated with
ischemia/reperfusion. Moreover, myeloperoxidase activity in the ischemic
myocardium was significantly lower than MAb R3.1-treated cats (0.4 +/- 0.1
versus 0.9 +/- 0.2 U/100 mg tissue, P < .05). CONCLUSIONS. These results
demonstrate that blocking L-selectin with DREG-200 exerts a significant
cardioprotective effect in a feline model of myocardial ischemia and
reperfusion, indicating that L-selectin plays a significant role in
mediating PMN accumulation and PMN-induced endothelial and myocardial
injury after ischemia and reperfusion.
ARTICLES
Monoclonal antibody to L-selectin attenuates neutrophil accumulation and protects ischemic reperfused cat myocardium
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa 19107-6799.
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