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代谢适应支持巨噬细胞在有限的氧气环境中增强胞葬作用
作者:小柯机器人 发布时间:2022/12/31 23:18:53

美国纪念斯隆凯特琳癌症研究所Justin S.A. Perry团队发现,代谢适应支持巨噬细胞在有限的氧气环境中增强胞葬作用。该研究于2022年12月29日在线发表于国际一流学术期刊《细胞—代谢》。

研究人员发现巨噬细胞在长期(慢性)生理性缺氧的情况下显示出更强的胞葬作用,其特点是增加内化和加速凋亡细胞(AC)的降解。转录和翻译分析显示,慢性生理性缺氧会诱发两种不同但互补的状态。第一种,“启动”状态,包括同时转录和翻译AC-naive巨噬细胞中的代谢程序,这些程序在胞葬作用时持续存在。第二种,“准备好”状态,包括AC-naive巨噬细胞中胞葬作用功能程序的转录,但不是翻译,这些程序在胞葬作用中被翻译。
 
从机制上讲,巨噬细胞有效地将葡萄糖通入非经典的磷酸戊糖途径(PPP)循环,从而提高NADPH的产生。PPP产生的NADPH通过确保吞噬体的成熟和氧化还原的平衡,直接支持生理性缺氧下增强的胞葬作用。因此,居住在生理性缺氧下的巨噬细胞采取支持细胞健康的状态,并确保快速和安全地执行基本的平衡功能。
 
据悉,AC的清除(胞葬)是由居住在恶劣生理环境中的吞噬细胞,如巨噬细胞进行的。
 
附:英文原文

Title: Metabolic adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments

Author: Ya-Ting Wang, Alissa J. Trzeciak, Waleska Saitz Rojas, Pedro Saavedra, Yan-Ting Chen, Rachel Chirayil, Jon Iker Etchegaray, Christopher D. Lucas, Daniel J. Puleston, Kayvan R. Keshari, Justin S.A. Perry

Issue&Volume: 2022-12-29

Abstract: Apoptotic cell (AC) clearance (efferocytosis) is performed by phagocytes, such asmacrophages, that inhabit harsh physiological environments. Here, we find that macrophagesdisplay enhanced efferocytosis under prolonged (chronic) physiological hypoxia, characterizedby increased internalization and accelerated degradation of ACs. Transcriptional andtranslational analyses revealed that chronic physiological hypoxia induces two distinctbut complimentary states. The first, “primed” state, consists of concomitant transcriptionand translation of metabolic programs in AC-naive macrophages that persist duringefferocytosis. The second, “poised” state, consists of transcription, but not translation,of phagocyte function programs in AC-naive macrophages that are translated duringefferocytosis. Mechanistically, macrophages efficiently flux glucose into a noncanonicalpentose phosphate pathway (PPP) loop to enhance NADPH production. PPP-derived NADPHdirectly supports enhanced efferocytosis under physiological hypoxia by ensuring phagolysosomalmaturation and redox homeostasis. Thus, macrophages residing under physiological hypoxiaadopt states that support cell fitness and ensure performance of essential homeostaticfunctions rapidly and safely.

DOI: 10.1016/j.cmet.2022.12.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00542-3

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:31.373
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx