Macrophages Mediate the Repair of Brain Vascular Rupture through Direct Physical Adhesion and Mechanical Traction
Macrophages Mediate the Repair of Brain Vascular Rupture through Direct Physical Adhesion and Mechanical Traction
复制标题
巨噬细胞通过直接物理粘附和机械牵引介导脑血管破裂的修复
DOI：
10.1016/j.immuni.2016.03.008
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发表时间：
2016-05-17
期刊：
影响因子：
32.4
通讯作者：
Luo, Lingfei
中科院分区：
文献类型：
--
作者：
Liu, Chi;Wu, Chuan;Luo, Lingfei
出血性中风和脑微出血由脑血管破裂引起。这种破裂的快速修复是最有前途的治疗方法。由于缺乏高分辨率的体内实时研究，脑血管修复中涉及的动态细胞事件仍然未知。在这里，我们已经开发了一个脑血管破裂系统，在斑马鱼通过使用多光子激光，产生一个损伤与两个内皮末端。在体内的时间推移成像显示，巨噬细胞到达病变和延长丝状伪足或板状伪足物理粘附到两个内皮末端。这种巨噬细胞产生机械牵引力来拉动内皮末端并促进它们的结扎，从而介导破裂的修复。微丝解聚和磷脂酰肌醇3-激酶或Rac 1活性的抑制都破坏了巨噬细胞-内皮细胞粘附和脑血管修复受损。我们的研究揭示了巨噬细胞通过直接物理粘附和机械牵引介导脑血管破裂修复的迄今为止意想不到的作用。
Hemorrhagic stroke and brain microbleeds are caused by cerebrovascular ruptures. Fast repair of such ruptures is the most promising therapeutic approach. Due to a lack of high-resolution in vivo real-time studies, the dynamic cellular events involved in cerebrovascular repair remain unknown. Here, we have developed a cerebrovascular rupture system in zebrafish by using multi-photon laser, which generates a lesion with two endothelial ends. In vivo time-lapse imaging showed that a macrophage arrived at the lesion and extended filopodia or lamellipodia to physically adhere to both endothelial ends. This macrophage generated mechanical traction forces to pull the endothelial ends and facilitate their ligation, thus mediating the repair of the rupture. Both depolymerization of microfilaments and inhibition of phosphatidylinositide 3-kinase or Rac1 activity disrupted macrophage-endothelial adhesion and impaired cerebrovascular repair. Our study reveals a hitherto unexpected role for macrophages in mediating repair of cerebrovascular ruptures through direct physical adhesion and mechanical traction.