P-selectin-dependent inhibition of thrombosis during venous stasis
P-selectin-dependent inhibition of thrombosis during venous stasis
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DOI：
10.1161/01.atv.20.11.2483
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发表时间：
2000-11-01
影响因子：
8.7
通讯作者：
Schaub, RG
中科院分区：
文献类型：
--
作者：
Eppihimer, MJ;Schaub, RG
白细胞粘附、跨内皮迁移和淤滞是深静脉血栓形成发病机制的重要组成部分。在暴露和闭塞颈静脉之前，用生理盐水、重组可溶形式的P-选择素糖蛋白配体-1（rPSGL-Ig）或E-和L-选择素抗体（EL-246）处理麻醉猫。闭塞2或6小时后，用缓冲液灌注颈静脉，固定，并准备用于扫描电子显微镜。在接受生理盐水的猫中，闭塞2和6小时产生中等水平的白细胞和血小板粘附以及内皮细胞损伤。用rPSGL-Ig或EL-246处理猫与不处理相比，对细胞粘附和内皮细胞损伤的程度没有明显影响。闭塞6小时后，在未处理的静脉中观察到附壁血栓的存在，并通过扫描电子显微镜证实。用rPSGL-Ig完全（4.0 mg/kg）或部分（1.0 mg/kg）预处理猫防止颈静脉中血栓的发生。静脉停滞6小时后，rPSGL-Ig治疗可减少血栓形成，对白细胞介导的内皮细胞损伤无任何影响，提示该蛋白具有抗血栓形成作用机制。
Leukocyte adhesion, transendothelial migration, and stasis are important components in the pathogenesis of deep vein thrombosis. Anesthetized cats were treated with saline, a recombinant soluble form of P-selectin glycoprotein ligand-1 (rPSGL-Ig), or an E- and L-selectin antibody (EL-246) before exposure and occlusion of a jugular vein. After 2 or 6 hours of occlusion, jugular veins were perfused with buffer, fixed, and prepared for scanning electron microscopy. In cats receiving saline, 2 and 6 hours of occlusion produced moderate levels of leukocyte and platelet adhesion and endothelial cell injury. Treatment of cats with rPSGL-Ig or EL-246 had no apparent effect on the magnitude of cell adhesion and endothelial cell injury compared with no treatment. After 6 hours of occlusion, the presence of a mural thrombus in untreated veins was observed and confirmed by scanning electron microscopy. Pretreatment of cats with rPSGL-Ig completely (4.0 mg/kg) or partially (1.0 mg/kg) prevented the occurrence of thrombi in the jugular veins. The reduction in thrombosis by rPSGL-Ig treatment after 6 hours of venous stasis, in the absence of any effect on leukocyte-mediated endothelial cell injury, suggests an antithrombotic mechanism of action for this protein.