Efferocytosis induces macrophage proliferation to help resolve tissue injury.

Autor:	Gerlach BD; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA., Ampomah PB; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA., Yurdagul A Jr; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA., Liu C; Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Lauring MC; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA., Wang X; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA., Kasikara C; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA., Kong N; Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Shi J; Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Tao W; Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Tabas I; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Physiology, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: iat1@cumc.columbia.edu.
Jazyk:	angličtina
Zdroj:	Cell metabolism [Cell Metab] 2021 Dec 07; Vol. 33 (12), pp. 2445-2463.e8. Date of Electronic Publication: 2021 Nov 15.
DOI:	10.1016/j.cmet.2021.10.015
Abstrakt:	Apoptotic cell clearance by macrophages (efferocytosis) promotes resolution signaling pathways, which can be triggered by molecules derived from the phagolysosomal degradation of apoptotic cells. We show here that nucleotides derived from the hydrolysis of apoptotic cell DNA by phagolysosomal DNase2a activate a DNA-PKcs-mTORC2/Rictor pathway that increases Myc to promote non-inflammatory macrophage proliferation. Efferocytosis-induced proliferation expands the pool of resolving macrophages in vitro and in mice, including zymosan-induced peritonitis, dexamethasone-induced thymocyte apoptosis, and atherosclerosis regression. In the dexamethasone-thymus model, hematopoietic Rictor deletion blocked efferocytosing macrophage proliferation, apoptotic cell clearance, and tissue resolution. In atherosclerosis regression, silencing macrophage Rictor or DNase2a blocked efferocyte proliferation, apoptotic cell clearance, and plaque stabilization. In view of previous work showing that other types of apoptotic cell cargo can promote resolution in individual efferocytosing macrophages, the findings here suggest that signaling-triggered apoptotic cell-derived nucleotides can amplify this benefit by increasing the number of these macrophages. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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