دورية أكاديمية

Metabolic adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments.

التفاصيل البيبلوغرافية
العنوان: Metabolic adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments.
المؤلفون: Wang YT; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Trzeciak AJ; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Rojas WS; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Saavedra P; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Chen YT; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Chirayil R; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Etchegaray JI; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA., Lucas CD; University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, Scotland, UK; Institute for Regeneration and Repair, Edinburgh BioQuarter, Edinburgh, Scotland, UK., Puleston DJ; Bloomberg, Kimmel Institute of Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA., Keshari KR; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Perry JSA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY, USA. Electronic address: perryj@mskcc.org.
المصدر: Cell metabolism [Cell Metab] 2023 Feb 07; Vol. 35 (2), pp. 316-331.e6. Date of Electronic Publication: 2022 Dec 29.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101233170 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-7420 (Electronic) Linking ISSN: 15504131 NLM ISO Abbreviation: Cell Metab Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, Mass. : Cell Press, c2005-
مواضيع طبية MeSH: Oxygen*/metabolism , Macrophages*/metabolism, Humans ; NADP/metabolism ; Phagocytosis ; Hypoxia/metabolism ; Apoptosis/physiology
مستخلص: Apoptotic cell (AC) clearance (efferocytosis) is performed by phagocytes, such as macrophages, that inhabit harsh physiological environments. Here, we find that macrophages display enhanced efferocytosis under prolonged (chronic) physiological hypoxia, characterized by increased internalization and accelerated degradation of ACs. Transcriptional and translational analyses revealed that chronic physiological hypoxia induces two distinct but complimentary states. The first, "primed" state, consists of concomitant transcription and translation of metabolic programs in AC-naive macrophages that persist during efferocytosis. The second, "poised" state, consists of transcription, but not translation, of phagocyte function programs in AC-naive macrophages that are translated during efferocytosis. Mechanistically, macrophages efficiently flux glucose into a noncanonical pentose phosphate pathway (PPP) loop to enhance NADPH production. PPP-derived NADPH directly supports enhanced efferocytosis under physiological hypoxia by ensuring phagolysosomal maturation and redox homeostasis. Thus, macrophages residing under physiological hypoxia adopt states that support cell fitness and ensure performance of essential homeostatic functions rapidly and safely.
Competing Interests: Declaration of interests K.R.K. serves on the scientific advisory board of NVision Imaging Technologies. J.S.A.P. and K.R.K. holds patents related to imaging and modulation of cellular metabolism.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: R00 CA237728 United States CA NCI NIH HHS; L30 CA274750 United States CA NCI NIH HHS; DP2 GM146337 United States GM NIGMS NIH HHS; T32 AI007496 United States AI NIAID NIH HHS; T32 CA009149 United States CA NCI NIH HHS; R01 CA248364 United States CA NCI NIH HHS; P30 CA008748 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: apoptotic cell clearance; cellular adaptation; efferocytosis; homeostasis; metabolism; oxygen; pentose phosphate pathway; physiological hypoxia
المشرفين على المادة: S88TT14065 (Oxygen)
53-59-8 (NADP)
تواريخ الأحداث: Date Created: 20221230 Date Completed: 20230210 Latest Revision: 20240322
رمز التحديث: 20240322
مُعرف محوري في PubMed: PMC9908853
DOI: 10.1016/j.cmet.2022.12.005
PMID: 36584675
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-7420
DOI:10.1016/j.cmet.2022.12.005