Myc-nick promotes efferocytosis through M2 macrophage polarization during resolution of inflammation

• Published in: The FASEB journal Vol. 32; no. 10; p. 5312
• Main Authors: Zhong, Xiancai, Lee, Ha-Na, Kim, Seung Hyeon, Park, Sin-Aye, Kim, Wonki, Cha, Young-Nam, Surh, Young-Joon
• Format: Journal Article
• Language: English
• Published: United States 01.10.2018
• Subjects: Acetylation; Animals; Antigens, Differentiation - immunology; Bone Marrow Cells - immunology; Bone Marrow Cells - pathology; Histone Acetyltransferases - immunology; Inflammation - immunology; Inflammation - pathology; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - pathology; Mice; p300-CBP Transcription Factors - immunology; Proto-Oncogene Proteins c-myc - immunology; Tubulin - immunology; phagocytosis; tubulin acetylation; c-Myc; peritonitis
• ISSN: 1530-6860
• DOI: 10.1096/fj.201800223r

A key event required for effective resolution of inflammation is efferocytosis, which is defined as phagocytic removal of apoptotic cells mostly by macrophages acquiring an alternatively activated phenotype (M2). c-Myc has been reported to play a role in alternative activation of human macrophages and is proposed as one of the M2 macrophage markers. We found that M2-like peritoneal macrophages from zymosan A-treated mice exhibited a marked accumulation of Myc-nick, a truncated protein generated by a Calpain-mediated proteolytic cleavage of full-length c-Myc. Further, ectopic expression of Myc-nick in murine bone marrow-derived macrophages promoted the M2 polarization and, consequently, enhanced their efferocytic capability. Notably, Myc-nick-induced efferocytosis was found to be tightly associated with α-tubulin acetylation by K acetyltransferase 2a (Kat2a/Gcn5) activity. These findings suggest Myc-nick as a novel proresolving mediator that has a fundamental function in maintaining homeostasis under inflammatory conditions.-Zhong, X., Lee, H.-N., Kim, S. H., Park, S.-A., Kim, W., Cha, Y.-N., Surh, Y.-J. Myc-nick promotes efferocytosis through M2 macrophage polarization during resolution of inflammation.