Shi J, Kokubo Y, Wake K
Department of Anatomy, School of Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan.
Blood. 1998 Jul 15;92(2):520-8.
The role of P-selectin on polymorphonuclear leukocyte (PMN) adhesion-induced PMN elimination in the liver is unclear. Our objectives were to show the expression and distribution of P-selectin in rat liver, as well as to evaluate the changes in the modulation of the expression of P-selectin and its role in the accumulation and sequestration of PMNs. The intravenous administration of endotoxin markedly increased the expression of P-selectin on the venous and sinusoidal endothelial cells, as well as on the platelets trapped in the liver. Its expression peaked at 6 hours postinjection and was associated with a rapid increase in the aggregation and elimination of PMNs in the hepatic sinusoids. Combined treatment with an antibody to P-selectin or with low molecular weight heparin, a P-selectin antagonist, blocked the P-selectin, significantly reduced the arrest of PMNs, and delayed their removal in the liver. Pretreatment with gadolinium chloride inhibited phagocytosis of PMNs by the Kupffer cells, decreased the expression of P-selectin, and limited the hepatic accumulation of PMNs. Thus, P-selectin played a role in accumulation and elimination of PMNs from the liver. Results also suggest that activated Kupffer cells can modulate the expression of P-selectin in the liver and influence the homeostasis of PMNs in the circulation during acute inflammation.
P-选择素在肝脏中多形核白细胞（PMN）黏附诱导的PMN清除过程中的作用尚不清楚。我们的目的是展示P-选择素在大鼠肝脏中的表达和分布，以及评估P-选择素表达调节的变化及其在PMN聚集和滞留中的作用。静脉注射内毒素显著增加了静脉和窦状内皮细胞以及肝脏中捕获的血小板上P-选择素的表达。其表达在注射后6小时达到峰值，并与肝窦中PMN聚集和清除的快速增加相关。用抗P-选择素抗体或P-选择素拮抗剂低分子量肝素联合治疗可阻断P-选择素，显著减少PMN的滞留，并延迟其在肝脏中的清除。用氯化钆预处理可抑制库普弗细胞对PMN的吞噬作用，降低P-选择素的表达，并限制PMN在肝脏中的积累。因此，P-选择素在肝脏中PMN的积累和清除中发挥了作用。结果还表明，活化的库普弗细胞可调节肝脏中P-选择素的表达，并在急性炎症期间影响循环中PMN的稳态。
