Mulligan M S, Polley M J, Bayer R J, Nunn M F, Paulson J C, Ward P A
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
J Clin Invest. 1992 Oct;90(4):1600-7. doi: 10.1172/JCI116029.
Rapid translocation of P-selectin (GMP-140) from cytoplasmic granules to the cell membrane of endothelial cells promotes adhesive interactions with neutrophils which, when activated, damage the endothelium. The role of P-selectin in lung vascular endothelial injury in rats after systemic activation of complement by intravenous infusion of cobra venom factor has been assessed. Within 5-10 min after cobra venom factor infusion, the pulmonary vasculature demonstrated immunohistochemical expression of an epitope that reacts with anti-human P-selectin. Monoclonal antibody to human P-selectin blocked in vitro adherence of rat or human platelets (activated with thrombin) to neutrophils and was demonstrated to react with thrombin-activated rat platelets. The antibody did not react with rat neutrophils. In vivo, the antibody had strongly protective effects against cobra venom factor-induced pulmonary vascular injury as determined by permeability changes and hemorrhage. In parallel, lung myeloperoxidase content was greatly reduced and, by transmission electron microscopy, there was markedly diminished adherence of neutrophils to the pulmonary vascular endothelium and much diminished injury of endothelial cells, as defined by hemorrhage. These data indicate that anti-human P-selectin reacts with a pulmonary vascular antigen in rats and that this antigen is essential for the full expression of lung injury.
P-选择素（GMP-140）从细胞质颗粒快速转位至内皮细胞的细胞膜，促进了与中性粒细胞的黏附相互作用，而中性粒细胞被激活后会损伤内皮。本研究评估了静脉注射眼镜蛇毒因子全身激活补体后，P-选择素在大鼠肺血管内皮损伤中的作用。在注射眼镜蛇毒因子后5 - 10分钟内，肺血管显示出与抗人P-选择素反应的表位的免疫组化表达。抗人P-选择素单克隆抗体可阻断大鼠或人血小板（经凝血酶激活）与中性粒细胞的体外黏附，并被证明可与凝血酶激活的大鼠血小板反应。该抗体不与大鼠中性粒细胞反应。在体内，通过通透性变化和出血情况测定，该抗体对眼镜蛇毒因子诱导的肺血管损伤具有强烈的保护作用。同时，肺髓过氧化物酶含量大幅降低，并且通过透射电子显微镜观察，中性粒细胞与肺血管内皮的黏附明显减少，内皮细胞损伤（以出血定义）也显著减轻。这些数据表明，抗人P-选择素与大鼠肺血管中的一种抗原反应，且该抗原对于肺损伤的充分表达至关重要。
