Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction
Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction
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DOI：
10.1182/blood-2009-12-257832
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发表时间：
2010-08-05
期刊：
影响因子：
20.3
通讯作者：
Ruhrberg, Christiana
中科院分区：
文献类型：
--
作者：
Fantin, Alessandro;Vieira, Joaquim M.;Ruhrberg, Christiana
血管网络扩张分两步进行，首先是血管出芽，然后是血管吻合。血管出芽是由血管内皮生长因子（VEGF）的趋化梯度诱导的，其刺激尖端细胞突起。然而，目前尚不清楚哪些因素促进了相邻尖端细胞的融合，从而为现有的血管网络增加了新的回路。通过结合分析在巨噬细胞发育或VEGF信号传导中有缺陷的小鼠突变体与斑马鱼中的活体成像，我们现在表明巨噬细胞促进VEGF介导的尖端细胞诱导下游的尖端细胞融合。因此，巨噬细胞作为血管融合细胞发挥了迄今为止尚未确定和意想不到的作用。此外，我们还发现，血管发育所必需的促血管生成组织巨噬细胞与促进癌症血管生成开关的巨噬细胞之间存在惊人的分子相似性，包括细胞表面蛋白TIE 2和NRP 1的表达。我们的研究结果表明，组织巨噬细胞是抗血管生成治疗的靶点，但它们同样可以被用来刺激缺血性疾病的组织血管形成。（血。2010;116（5）：829-840）
Blood vessel networks expand in a 2-step process that begins with vessel sprouting and is followed by vessel anastomosis. Vessel sprouting is induced by chemotactic gradients of the vascular endothelial growth factor (VEGF), which stimulates tip cell protrusion. Yet it is not known which factors promote the fusion of neighboring tip cells to add new circuits to the existing vessel network. By combining the analysis of mouse mutants defective in macrophage development or VEGF signaling with live imaging in zebrafish, we now show that macrophages promote tip cell fusion downstream of VEGF-mediated tip cell induction. Macrophages therefore play a hitherto unidentified and unexpected role as vascular fusion cells. Moreover, we show that there are striking molecular similarities between the pro-angiogenic tissue macrophages essential for vascular development and those that promote the angiogenic switch in cancer, including the expression of the cell-surface proteins TIE2 and NRP1. Our findings suggest that tissue macrophages are a target for antiangiogenic therapies, but that they could equally well be exploited to stimulate tissue vascularization in ischemic disease. (Blood. 2010;116(5):829-840)