UCL Institute of Ophthalmology, University College London, London, United Kingdom.
Blood. 2010 Aug 5;116(5):829-40. doi: 10.1182/blood-2009-12-257832. Epub 2010 Apr 19.
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.
首先是血管发芽，然后是血管吻合。血管发芽是由血管内皮生长因子（VEGF）的趋化梯度诱导的，它刺激尖端细胞突起。然而，目前尚不清楚哪些因素促进相邻尖端细胞的融合，以将新的回路添加到现有的血管网络中。通过将缺乏巨噬细胞发育或 VEGF 信号的小鼠突变体的分析与斑马鱼的活体成像相结合，我们现在表明巨噬细胞在 VEGF 介导的尖端细胞诱导之后促进尖端细胞融合。因此，巨噬细胞在血管融合细胞方面发挥了迄今为止尚未被识别和预期的作用。此外，我们还表明，在血管发育中必不可少的促血管生成组织巨噬细胞和促进癌症血管生成开关的巨噬细胞之间存在显著的分子相似性，包括细胞表面蛋白 TIE2 和 NRP1 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，但它们同样可以被利用来刺激缺血性疾病中的组织血管生成。
