P-selectin and leukocyte microparticles are associated with venous thrombogenesis
P-selectin and leukocyte microparticles are associated with venous thrombogenesis
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DOI：
10.1016/s0741-5214(03)01033-4
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发表时间：
2003-11-01
影响因子：
4.3
通讯作者：
Wakefield, TW
中科院分区：
文献类型：
--
作者：
Myers, DD;Hawley, AE;Wakefield, TW
目的：已发现P-选择素抑制可限制静脉血栓形成。我们假设，升高水平的P-选择素将放大血栓形成，介导的促凝血微粒（MP）。方法：雄性小鼠（小家鼠，n659），20至25克，进行IVC结扎诱导血栓形成。组由野生型（WT）C57 BL/6对照、具有高循环水平的可溶性P-选择素的小鼠（CT）、P-选择素基因中断的敲除小鼠（PKO）以及E-和P-选择素基因中断的小鼠（EPKO）组成。另外的组用于评价P-sel拮抗剂（rPSGL-Ig）和针对PSGL-1的抗体在血栓形成时施用可溶性P-sel的ACT小鼠和WT小鼠中下调P-sel的作用的能力。在IVC结扎后第2天和第6天处死动物。采用荧光激活细胞双染扫描法和酶联免疫吸附试验（ELISA）检测血栓质量（TM）、静脉壁形态计量学和血清白细胞/血小板微粒（MP）。
Objectives: P-selectin inhibition has been found to limit venous thrombosis. We hypothesize that elevated levels of P-selectin will amplify thrombosis, mediated by procoagulant microparticles (MPs).Methods: Male mice (Mus musculus, n659), 20 to 25 grams, underwent IVC ligation to induce thrombosis. Groups consisted of wild type (WT) C57BL/6 controls, mice with high circulating levels of soluble P-selectin (CT), P-selectin gene-interrupted knockout mice (PKO), and E- and P-selectin gene-interrupted mice (EPKO). Additional groups were used to evaluate the ability of a P-sel antagonist (rPSGL-Ig) and an antibody directed against PSGL-1 to downregulate the effects of P-sel in ACT mice and WT mice administered soluble P-sel at time of thrombosis. Animals were sacrificed on days 2 and 6 after IVC ligation. Thrombus mass (TM), vein wall morphometrics, and serum leukocyte/platelet microparticles (MPs) were evaluated by means of double-stained fluorescence-activated cell scanning analysis, and soluble P- and E-sel protein determination by ELISA.Results: At days 2 and 6 in phase I of the experiment, significant differences (P