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》。
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
Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:31.373
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