Obligatory participation of macrophages in an angiopoietin 2-mediated cell death switch
Obligatory participation of macrophages in an angiopoietin 2-mediated cell death switch
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DOI：
10.1242/dev.012187
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发表时间：
2007-12-15
期刊：
影响因子：
4.6
通讯作者：
Lang, Richard A.
中科院分区：
文献类型：
--
作者：
Rao, Sujata;Lobov, Ivan B.;Lang, Richard A.
巨噬细胞在识别和吞噬死亡细胞方面具有关键作用。在某些情况下，巨噬细胞也会主动发出程序性细胞死亡的信号。在这里，我们展示了在发育规律的血管退化过程中，驻留的巨噬细胞是信号转换的强制性参与者，这种信号转换有利于死亡而不是生存。当信号配体血管生成素2具有抑制血管内皮细胞生存信号和刺激巨噬细胞产生Wnt配体的双重作用时，这种转换就会发生。作为对Wnt配体的响应，血管内皮细胞进入细胞周期，在没有生存信号的情况下，从细胞周期的G1期死亡。我们认为，这一机制代表了一种适应，以确保当细胞死亡发生时巨噬细胞及其处理能力在手边。
Macrophages have a critical function in the recognition and engulfment of dead cells. In some settings, macrophages also actively signal programmed cell death. Here we show that during developmentally scheduled vascular regression, resident macrophages are an obligatory participant in a signaling switch that favors death over survival. This switch occurs when the signaling ligand angiopoietin 2 has the dual effect of suppressing survival signaling in vascular endothelial cells (VECs) and stimulating Wnt ligand production by macrophages. In response to the Wnt ligand, VECs enter the cell cycle and in the absence of survival signals, die from G1 phase of the cell cycle. We propose that this mechanism represents an adaptation to ensure that the macrophage and its disposal capability are on hand when cell death occurs.