Blood:血小板-VWF通过刺激Tie-2防止白细胞外渗时血浆渗漏

2020-05-16 QQY MedSci原创

血小板通过与内皮VWF结合并释放Angpt1,阻止中性粒细胞穿出血管时血浆渗漏。 血小板释放的Angpt1刺激内皮细胞Tie-2,从而激活可增强皮质肌动蛋白束的GEF FGD5。

中性粒细胞外渗需要打开血管内皮屏障,但并不会自动导致血浆渗漏。收缩的肌动蛋白丝包围着血细胞外渗孔,使这个开口紧紧地封闭在迁移的中性粒细胞周围,从而防止血浆泄漏。

近期,Braun等明确了负责防止血浆渗漏的受体系统。研究人员通过荧光微球发现,沉默或失活内皮细胞的Tie-2都可以导致毛细血管后嗜中性粒细胞外渗部位的微静脉渗漏形成。血浆渗漏依赖于中性粒细胞外渗,因为中性粒细胞耗竭时就不存在血浆渗漏。

此外,研究人员还发现Cdc42 GTPase交换因子FGD5是Tie-2的下游靶点,在预防中性粒细胞外渗过程血浆渗漏中在发挥关键作用。在寻找Tie-2激动剂及其来源时,研究人员发现血小板源的血管生成素-1对于预防中性粒细胞引起的渗漏必不可少。

有趣的是,阻断血管性血友病因子(VWF)可导致血管在白细胞迁移过程中血浆渗漏,这表明血小板与内皮VWF之间的相互作用,可通过分泌血管生成素-1激活Tie-2,从而防止血细胞外渗诱导的血浆渗漏。

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    2020-12-10 dangious
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    2020-05-18 sunmin0219

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