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首页> 外文期刊>Current Biology: CB >Apoptotic cells induce a phosphatidyiserine-dependent homeostatic response from phagocytes
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Apoptotic cells induce a phosphatidyiserine-dependent homeostatic response from phagocytes

机译：凋亡细胞诱导吞噬细胞产生磷脂酰肌氨酸依赖性稳态反应

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摘要

Engulfment of apoptotic cells by phagocytes is important-throughout development and adult life [1, 2]. When phagocytes engulf apoptotic cells, they increase their cellular contents including cholesterol and phospholipids, but how the phagocytes respond to this increased load is poorly understood. Here, we identify one type of a phagocyte response, wherein the recognition of apoptotic cells triggers enhanced cholesterol efflux (to apolipoprotein A-I) from macrophages. Phosphatidylserine (PS) exposed on apoptotic cells was necessary and sufficient to stimulate the efflux response. A major mechanism for this enhanced efflux by macrophages was the upregulation of the mRNA and protein for ABCA1, a membrane transporter independently linked to cholesterol efflux as well as engulfment of apoptotic cells [3, 4]. This increase in phagocyte ABCA1 levels required the function of nuclear receptor LXR alpha/beta, a known regulator of cholesterol homeostasis in humans and mice [5]. Taken together, these data reveal a "homeostatic program" initiated in phagocytes that include a proximal membrane signaling event initiated by PS recognition, a downstream signaling event acting through nuclear receptors, and an effector arm involving upregulation of ABCA1, in turn promoting reverse cholesterol transport from the phagocytes. These data also have implications for macrophage handling of contents derived from apoptotic versus necrotic cells in atherosclerotic lesions [6].
机译：吞噬细胞吞噬凋亡细胞在整个发育和成年生活中都是重要的[1、2]。当吞噬细胞吞噬凋亡细胞时，它们会增加其细胞含量，包括胆固醇和磷脂，但人们对吞噬细胞如何应对这种增加的负荷却知之甚少。在这里，我们确定了一种吞噬细胞反应类型，其中凋亡细胞的识别触发了巨噬细胞胆固醇外排（对载脂蛋白A-I）的增强。暴露于凋亡细胞上的磷脂酰丝氨酸（PS）是必要且足以刺激外排反应的。巨噬细胞增强外排的主要机制是上调ABCA1的mRNA和蛋白质，ABCA1是一种与胆固醇外排独立相关的膜转运蛋白，并吞噬凋亡细胞[3，4]。吞噬细胞ABCA1水平的这种增加需要核受体LXR alpha / beta的功能，LXR alpha / beta是人和小鼠胆固醇稳态的已知调节剂[5]。综上所述，这些数据揭示了在吞噬细胞中启动的“稳态程序”，包括由PS识别启动的近端膜信号事件，通过核受体起作用的下游信号事件以及涉及ABCA1上调的效应子臂，进而促进胆固醇逆向转运。来自吞噬细胞。这些数据也对巨噬细胞处理动脉粥样硬化病变中凋亡和坏死细胞来源的内容有影响[6]。

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