Red blood cells mediate the onset of thrombosis in the ferric chloride murine model
Red blood cells mediate the onset of thrombosis in the ferric chloride murine model
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DOI：
10.1182/blood-2012-11-468983
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发表时间：
2013-05-02
期刊：
影响因子：
20.3
通讯作者：
Motto, David G.
中科院分区：
文献类型：
--
作者：
Barr, Justin D.;Chauhan, Anil K.;Motto, David G.
将氯化铁（FeCl 3）应用于暴露的血管被广泛用于在实验室小鼠中引发血栓形成。由于FeCl 3诱导内皮损伤和随后的血栓形成的机制知之甚少，我们使用扫描电子和明场活体显微镜观察原位发生的内皮损伤和血栓形成。与普遍接受的观点相反，在血栓形成的时间范围内，FeCl 3不会导致明显的内皮下暴露。此外，第一个粘附到FeCl 3处理的内皮表面的细胞是红细胞（RBC）而不是血小板。能量色散X射线光谱表明，铁离子主要定位于内皮相关的红细胞和红细胞衍生的结构，而不是内皮。随着时间点的持续，RBC衍生的结构迅速募集血小板，导致随后扩大和聚结的大复合物，迅速覆盖内皮表面。进一步的研究表明，红细胞粘附于内皮细胞既不需要血管性血友病因子也不需要血小板糖蛋白Ib-α受体（GPIb-α），GPIb-α的缺乏极大地消除了血小板向内皮相关红细胞材料的募集。这些发现阐明了FeCl 3介导的血栓形成的机制，并揭示了红细胞通过介导血小板粘附于完整内皮表面参与血栓形成的先前未被认识的能力。
Application of ferric chloride (FeCl3) to exposed blood vessels is widely used to initiate thrombosis in laboratory mice. Because the mechanisms by which FeCl3 induces endothelial injury and subsequent thrombus formation are little understood, we used scanning electron and brightfield intravital microscopy to visualize endothelial damage and thrombus formation occurring in situ. Contrary to generally accepted belief, FeCl3 does not result in appreciable subendothelial exposure within the time frame of thrombosis. Furthermore, the first cells to adhere to FeCl3-treated endothelial surfaces are red blood cells (RBCs) rather than platelets. Energy dispersive x-ray spectroscopy demonstrated that ferric ions predominantly localize to endothelial-associated RBCs and RBC-derived structures rather than to the endothelium. With continuing time points, RBC-derived structures rapidly recruit platelets, resulting in large complexes that subsequently enlarge and coalesce, quickly covering the endothelial surface. Further studies demonstrated that neither von Willebrand factor nor platelet glycoprotein Ib-alpha receptor (GPIb-alpha) is required for RBCs to adhere to the endothelium, and that deficiency of GPIb-alpha greatly abrogated the recruitment of platelets to the endothelial-associated RBC material. These findings illuminate the mechanisms of FeCl3-mediated thrombosis and reveal a previously unrecognized ability of RBCs to participate in thrombosis by mediating platelet adhesion to the intact endothelial surface.