美国哥伦比亚大学Ira Tabas、Arif Yurdagul Jr.等研究人员合作发现，凋亡细胞精氨酸的巨噬细胞代谢促进持续的胞葬作用和损伤修复。相关论文于2020年1月30日在线发表于国际学术期刊《细胞—代谢》。

据研究人员介绍，巨噬细胞对凋亡细胞（AC）的持续清除可防止坏死并促进损伤修复。目前尚不清楚如何促进持续的胞吞作用。

研究人员发现，该过程将吞噬货物的代谢从最初的胞吞事件联系到后续事件。他们发现，巨噬细胞精氨酸酶1（Arg1）和鸟氨酸脱羧酶（ODC）将AC来源的精氨酸和鸟氨酸代谢为腐胺，从而增强了持续的胞吞作用。腐胺增强HuR介导的Dbl（编码GTP交换因子）的mRNA稳定性，从而激活肌动蛋白调节性Rac1，以促进随后的AC内吞。在第一个AC摄取后，抑制该途径的任何一步都能抑制第二个AC的內吞，而添加腐胺可挽救该缺陷。缺乏髓样Arg1或ODC小鼠体内的胞吞作用和动脉粥样硬化消退都有缺陷，而腐胺的治疗可促进动脉粥样硬化的消退。因此，AC来源代谢产物的巨噬细胞代谢可实现最佳的持续性胞葬作用和损伤修复。

附：英文原文

Title: Macrophage Metabolism of Apoptotic Cell-Derived Arginine Promotes Continual Efferocytosis and Resolution of Injury

Author: Arif Yurdagul, Manikandan Subramanian, Xiaobo Wang, Scott B. Crown, Olga R. Ilkayeva, Lancia Darville, Gopi K. Kolluru, Christina C. Rymond, Brennan D. Gerlach, Ze Zheng, George Kuriakose, Christopher G. Kevil, John M. Koomen, John L. Cleveland, Deborah M. Muoio, Ira Tabas

Issue&Volume: January 30, 2020

Abstract: Continual efferocytic clearance of apoptotic cells (ACs) by macrophages prevents necrosisand promotes injury resolution. How continual efferocytosis is promoted is not clear.Here, we show that the process is optimized by linking the metabolism of engulfedcargo from initial efferocytic events to subsequent rounds. We found that continualefferocytosis is enhanced by the metabolism of AC-derived arginine and ornithine toputrescine by macrophage arginase 1 (Arg1) and ornithine decarboxylase (ODC). Putrescineaugments HuR-mediated stabilization of the mRNA encoding the GTP-exchange factor Dbl,which activates actin-regulating Rac1 to facilitate subsequent rounds of AC internalization.Inhibition of any step along this pathway after first-AC uptake suppresses second-ACinternalization, whereas putrescine addition rescues this defect. Mice lacking myeloidArg1 or ODC have defects in efferocytosis in vivo and in atherosclerosis regression, while treatment with putrescine promotes atherosclerosisresolution. Thus, macrophage metabolism of AC-derived metabolites allows for optimalcontinual efferocytosis and resolution of injury.

DOI: 10.1016/j.cmet.2020.01.001

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30001-2