Vascular sprouts induce local attraction of proangiogenic neutrophils
Vascular sprouts induce local attraction of proangiogenic neutrophils
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DOI：
10.1189/jlb.1ma0117-018r
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发表时间：
2017-09-01
影响因子：
5.5
通讯作者：
Phillipson, Mia
中科院分区：
文献类型：
--
作者：
Christoffersson, Gustaf;Lomei, Jalal;Phillipson, Mia
血管生成，即新血管的生长，是一个复杂的过程，需要许多不同的细胞类型，生长因子和趋化因子的协调。在这个过程中，一些最近被承认的演员是免疫细胞。它们在缺氧部位积累，但这种运输的动力学、动力学和调节尚不清楚。在这项研究中，我们使用活体和活细胞成像来了解中性粒细胞和巨噬细胞如何在血管生成部位迁移和行为。我们开发了两种可重复的血管生成模型：一种是将分离的缺氧胰岛移植到小鼠提睾肌中，另一种是将小鼠主动脉环与中性粒细胞体外共培养。缺氧部位的体内成像显示中性粒细胞和巨噬细胞的募集，这是平行发生的，其中一个亚群的消耗不影响另一个亚群的积累。我们发现，通过细胞追踪和统计分析，中性粒细胞以定向方式迁移到胰岛周围的血管生成热点，在那里发生内皮发芽，这在血管生成的体外模型中得到证实，并且依赖于CXCL12信号传导。中性粒细胞和新生血管之间的密切相互作用是普遍的，中性粒细胞耗竭极大地阻碍了血管生长。大血管运动性较差，并在新生血管周围获得支持性位置。在这里，我们提出了两种新的在体内和体外成像模型来研究白细胞的行为和行动在血管生成。这些模型揭示了缺氧部位的中性粒细胞迁移是由萌芽内皮发出的信号引导的，这些免疫细胞聚集在血管生长发生的血管生成热点。
Angiogenesis, the growth of new blood vessels, is a complex process requiring the orchestration of numerous different cell types, growth factors, and chemokines. Some of the recently acknowledged actors in this process are immune cells. They accumulate at hypoxic sites, but the kinetics, dynamics, and regulation of that trafficking are unknown. In this study, we used intravital and live cell imaging to understand how neutrophils and macrophages migrate and behave at angiogenic sites. We developed two reproducible models of angiogenesis: one by transplanting isolated and hypoxic pancreatic islets into the cremaster muscles of mice, and another by in vitro coculturing of mouse aortic rings with neutrophils. In vivo imaging of the hypoxic site revealed recruitment of neutrophils and macrophages, which occurred in parallel, with depletion of one subset not affecting the accumulation of the other. We found, by cell tracking and statistical analyses, that neutrophils migrated in a directional manner to angiogenic hotspots around the islet where endothelial sprouting occurs, which was confirmed in the in vitro model of angiogenesis and is dependent on CXCL12 signaling. Intimate interactions between neutrophils and neovessels were prevalent, and neutrophil depletion greatly hampered vessel growth. Macrophages were less motile and attained supportive positions around the neovessels. Here, we present two novel in vivo and in vitro imaging models to study leukocyte behavior and actions during angiogenesis. These models unveiled that neutrophil migration at a hypoxic site was guided by signals emanating from sprouting endothelium where these immune cells gathered at angiogenic hotspots at which vascular growth occurred.