TNT-Induced Phagocytosis: Tunneling Nanotubes Mediate the Transfer of Pro-Phagocytic Signals From Apoptotic to Viable Cells.

TNT-Induced Phagocytosis: Tunneling Nanotubes Mediate the Transfer of Pro-Phagocytic Signals From Apoptotic to Viable Cells.
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DOI:
10.1002/jcp.25584
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发表时间:
2017-09
影响因子:
5.6
通讯作者:
Wang X
Wang X
中科院分区:
生物学2区
文献类型:
--
作者:
Bittins M;Wang X

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磷脂酰丝氨酸(PS)暴露在凋亡细胞的表面膜上,触发吞噬受体的募集,随后导致吞噬细胞的摄取。在这里,我们描述了凋亡细胞如何使用细胞间膜纳米管将暴露的PS转移到相邻的活细胞,从而在活细胞上存款“吃我”标签。Tunneling nanotubes(TNT)将UV处理的凋亡大鼠嗜铬细胞瘤PC 12细胞与相邻的未处理细胞连接起来。这些TNT由PS暴露的质膜组成,并促进膜从凋亡细胞转移到活细胞。其他促吞噬信号,如氧化磷脂和钙网蛋白,也转移到活细胞。此外,存在于活细胞质膜上的抗吞噬信号CD 47被转移的PS膜掩蔽。共聚焦成像显示,当活的PC 12细胞与UV处理的PC 12细胞共培养时,鼠RAW264.7巨噬细胞对活的PC 12细胞的吞噬作用增加。用50 nM细胞松弛素D处理将消除TNT并相应地抑制活细胞的这种吞噬作用。我们的研究表明,暴露的PS膜通过TNT从凋亡细胞传递到活细胞。这种转移的膜可以作为巨噬细胞的促吞噬信号,在凋亡细胞附近诱导活细胞的吞噬作用。J.细胞。Physiol.232:2271-2279,2017.© 2016作者。细胞生理学杂志由Wiley Periodicals Inc.出版。
The exposure of phosphatidylserine (PS) on the surface membrane of apoptotic cells triggers the recruitment of phagocytic receptors and subsequently results in uptake by phagocytes. Here we describe how apoptotic cells can use intercellular membrane nanotubes to transfer exposed PS to neighboring viable cells, and thus deposit an “eat‐me” tag on the viable cells. Tunneling nanotubes (TNTs) connected UV‐treated apoptotic rat pheochromocytoma PC12 cells with neighboring untreated cells. These TNTs were composed of PS‐exposed plasma membrane and facilitated the transfer of the membrane from apoptotic to viable cells. Other pro‐phagocytic signals, such as oxidized phospholipids and calreticulin, were also transferred to viable cells. In addition, anti‐phagocytic signal CD47 presenting on the plasma membrane of viable cells was masked by the transferred PS‐membrane. Confocal imaging revealed an increase of phagocytosis of viable PC12 cells by murine RAW264.7 macrophages when the viable PC12 cells were cocultured with UV‐treated PC12 cells. Treatment with 50 nM cytochalasin D would abolish TNTs and correspondingly inhibit this phagocytosis of the viable cells. Our study indicates that exposed‐PS membrane is delivered from apoptotic to viable cells through TNTs. This transferred membrane may act as a pro‐phagocytic signal for macrophages to induce phagocytosis of viable cells in a situation where they are in the vicinity of apoptotic cells. J. Cell. Physiol. 232: 2271–2279, 2017. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals Inc.