Eosinophils are a major intravascular location for tissue factor storage and exposure
Eosinophils are a major intravascular location for tissue factor storage and exposure
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DOI：
10.1182/blood-2006-02-004945
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发表时间：
2007-02-01
期刊：
影响因子：
20.3
通讯作者：
Engelmann, Bernd
中科院分区：
文献类型：
--
作者：
Moosbauer, Christine;Morgenstern, Eberhard;Engelmann, Bernd
通过免疫电镜扫描血细胞祖细胞中是否存在凝血起始蛋白组织因子（TF）。因此，在嗜酸性粒细胞的前体细胞中观察到大量TF表达。TF水平在嗜碱性前体细胞中较低，在中性粒细胞祖细胞中几乎检测不到。在外周血中立即处理，以避免TF基因的激活，成熟的嗜酸性粒细胞被发现相当表达TF，独特的粒细胞和单核细胞组分。TF优先定位于静息嗜酸性粒细胞的特异性颗粒。血小板活化因子（PAF），更明显的是，粒细胞-巨噬细胞集落刺激因子（GM-CSF）加PAF，引起预先形成的TF易位到嗜酸性粒细胞细胞膜。GM-CSF/PAF也能增加TF转录水平。活化的嗜酸性粒细胞表现出促凝血活性，TF抑制可消除该活性。用特异性抗体靶向TF的细胞外结构域显著抑制了嗜酸性粒细胞穿过IL-4激活的内皮的初始阶段。嗜酸性粒细胞滚动和牢固粘附不受影响。这表明TF特异性地促进嗜酸性粒细胞的早期跨内皮迁移。总之，嗜酸性粒细胞在成熟过程中保持高TF表达，提供了血液中预先形成的TF的主要来源，这可能与嗜酸性粒细胞增多促进的血栓形成有关。
Blood cell progenitors were scanned for the presence of the coagulation starter protein tissue factor (TF) by immunoelectron microscopy. Thereby, substantial TF expression was observed in the precursor cells of eosinophils. TF levels were lower in basophil precursors and barely detectable in neutrophil progenitors. In peripheral blood immediately processed to avoid activation of the TF gene, mature eosinophils were found to considerably express TF, unique among the granulocyte and monocyte fractions. TF was preferentially located in the specific granules in resting eosinophils. Platelet-activating factor (PAF), and more pronounced, granulocyte-macrophage colony-stimulating factor (GM-CSF) plus PAF, caused translocation of preformed TF to the eosinophil cell membrane. GM-CSF/PAF also increased the TF transcript levels. The activated eosinophils exhibited procoagulant activity that was abrogated by TF inhibition. Targeting the extracellular domain of TF with specific antibodies markedly suppressed the initial phase of the eosinophil passage across the IL-4-activated endothelium. Eosinophil rolling and firm adhesion remained unaffected. This suggests that TF specifically facilitates the early transendothelial migration of the eosinophils. In summary, eosinophils maintain a high TF expression during maturation, providing a main source of preformed TF in blood, which might be relevant for the thrombogenesis promoted by hypereosinophilic conditions.