Lefer D J, Flynn D M, Anderson D C, Buda A J
Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Am J Physiol. 1996 Dec;271(6 Pt 2):H2421-9. doi: 10.1152/ajpheart.1996.271.6.H2421.
Neutrophil-endothelial cell interactions are mediated by a number of cell adhesion proteins. We investigated the effects of inhibition of P-selectin and intercellular adhesion molecule-1 (ICAM-1), individually or in combination, in the ischemic-reperfused canine myocardium. Monoclonal antibodies PB1.3 (anti-P-selectin) and CL 18/6 (anti-ICAM-1) were administered to dogs subjected to coronary artery occlusion and reperfusion. After reperfusion, untreated dogs experienced a 61% decline (P < 0.01 vs. baseline) in myocardial blood flow and a ninefold increase in ischemic zone neutrophil accumulation (4.7 +/- 0.9 U/100 mg tissue myeloperoxidase activity). In contrast, PB1.3 and CL 18/6 administered individually preserved myocardial blood flow (11 and 24% decrease from baseline, respectively, both P < 0.01 vs. saline), and significantly attenuated myeloperoxidase activity (1.4 +/- 0.3 and 1.5 +/- 0.26 U/100 mg tissue, respectively, both P < 0.01 vs. saline). PB1.3 and CL 18/6 in combination resulted in significant coronary vascular and myocardial protection that was not superior to treatment with either antibody alone. Thus the coadministration of anti-P-selectin and anti-ICAM-1 monoclonal antibodies does not enhance the degree of myocardial protection in this model of reperfusion injury.
中性粒细胞与内皮细胞的相互作用由多种细胞黏附蛋白介导。我们研究了单独或联合抑制P-选择素和细胞间黏附分子-1（ICAM-1）对犬缺血再灌注心肌的影响。将单克隆抗体PB1.3（抗P-选择素）和CL 18/6（抗ICAM-1）给予经历冠状动脉闭塞和再灌注的犬。再灌注后，未治疗的犬心肌血流量下降61%（与基线相比，P<0.01），缺血区中性粒细胞积聚增加9倍（4.7±0.9 U/100 mg组织髓过氧化物酶活性）。相比之下，单独给予PB1.3和CL 18/6可保留心肌血流量（分别较基线下降11%和24%，两者与生理盐水相比均P<0.01），并显著降低髓过氧化物酶活性（分别为1.4±0.3和1.5±0.26 U/100 mg组织，两者与生理盐水相比均P<0.01）。联合使用PB1.3和CL 18/6可产生显著的冠状动脉血管和心肌保护作用，但并不优于单独使用任何一种抗体治疗。因此，在这种再灌注损伤模型中，联合给予抗P-选择素和抗ICAM-1单克隆抗体并不会增强心肌保护程度。
