INSERM (Institut National de la Santé Et de la Recherche Médicale), U858- I2MR, Toulouse, France.
J Thromb Haemost. 2010 Dec;8(12):2810-9. doi: 10.1111/j.1538-7836.2010.04088.x.
Microparticles (MPs) released by activated or apoptotic cells increase in number in the blood of subjects with vascular or metabolic diseases and may contribute to thrombotic complications.
In this study, we investigated whether MPs promoted platelet recruitment to endothelial cells in flow conditions, and by which mechanism.
Human umbilical vein endothelial cells (HUVECs) grown in microslide perfusion chambers were exposed to MPs prepared in vitro from HUVECs, monocytes or platelets.
Videomicroscopy of DIOC-labelled blood perfused at arterial rate on human umbilical vein ECs demonstrated that, irrespective of their cell origin, MPs promoted the formation of platelet strings at the surface of HUVECs. This platelet/endothelial cell interaction was dependent on von Willebrand factor (VWF) expression at the HUVEC surface and involved Glycoprotein Ib and P-selectin. Interestingly, HUVECs internalized MPs within a few hours through a process involving anionic phospholipids, lactadherin and αvβ3 integrin. This uptake generated the production of reactive oxygen species via the xanthine/xanthine oxidase system (inhibited by allopurinol and the ROCK inhibitor Y-27632) and the NADPH oxidase (inhibited by SOD). Reactive oxygen species appeared essential for VWF expression at the endothelial cell surface and subsequent platelet/endothelial cell interaction under flow. The pathophysiological relevance of this process is underlined by the fact that circulating MPs from Type I diabetic patients induced platelet/endothelial cell interaction under flow, with an intensity correlated with the severity of the vasculopathy.
激活或凋亡细胞释放的微粒（MPs）在患有血管或代谢疾病的患者的血液中数量增加，可能导致血栓并发症。
在这项研究中，我们研究了 MPs 在流动条件下是否促进血小板向内皮细胞的募集，以及通过哪种机制。
在微室灌注培养皿中生长的人脐静脉内皮细胞（HUVECs）暴露于体外从 HUVECs、单核细胞或血小板制备的 MPs。
在动脉速率下对人脐静脉 ECs 进行 DIOC 标记的血液灌注的视频显微镜检查表明，无论其细胞来源如何，MPs 均可促进血小板在 HUVEC 表面形成串珠。这种血小板/内皮细胞相互作用依赖于 HUVEC 表面的血管性血友病因子（VWF）表达，并涉及糖蛋白 Ib 和 P-选择素。有趣的是，HUVECs 在数小时内通过涉及阴离子磷脂、乳粘连蛋白和 αvβ3 整合素的过程内化 MPs。这种摄取通过黄嘌呤/黄嘌呤氧化酶系统（被别嘌呤醇和 ROCK 抑制剂 Y-27632 抑制）和 NADPH 氧化酶（被 SOD 抑制）产生活性氧物质。活性氧物质对于 VWF 在内皮细胞表面的表达以及随后在流动条件下的血小板/内皮细胞相互作用至关重要。这一过程的病理生理相关性体现在来自 1 型糖尿病患者的循环 MPs 在流动下诱导血小板/内皮细胞相互作用，其强度与血管病变的严重程度相关。
