PDF(Pubmed)
Abstract：
Acute lung injury (ALI) is one of the life-threatening complications of sepsis, and macrophage polarization plays a crucial role in the sepsis-associated ALI. However, the regulatory mechanisms of macrophage polarization in ALI and in the development of inflammation are largely unknown. In this study, we demonstrated that macrophage polarization occurs in sepsis-associated ALI and is accompanied by mitochondrial dysfunction and inflammation, and a decrease of PRDX3 promotes the initiation of macrophage polarization and mitochondrial dysfunction. Mechanistically, PRDX3 overexpression promotes M1 macrophages to differentiate into M2 macrophages, and enhances mitochondrial functional recovery after injury by reducing the level of glycolysis and increasing TCA cycle activity. In conclusion, we identified PRDX3 as a critical hub integrating oxidative stress, inflammation, and metabolic reprogramming in macrophage polarization. The findings illustrate an adaptive mechanism underlying the link between macrophage polarization and sepsis-associated ALI.
摘要：
急性肺损伤(ALI)是脓毒症危及生命的并发症之一。巨噬细胞极化在脓毒症相关ALI中起着至关重要的作用。然而,ALI和炎症发展中巨噬细胞极化的调节机制尚不清楚.在这项研究中,我们证明，巨噬细胞极化发生在脓毒症相关的ALI中，并伴有线粒体功能障碍和炎症，PRDX3的减少促进巨噬细胞极化和线粒体功能障碍的启动。机械上,PRDX3过表达促进M1巨噬细胞向M2巨噬细胞分化,并通过降低糖酵解水平和增加TCA循环活性来增强损伤后线粒体功能恢复。总之,我们确定PRDX3是整合氧化应激的关键枢纽，炎症,和巨噬细胞极化中的代谢重编程。这些发现说明了巨噬细胞极化和脓毒症相关ALI之间联系的适应性机制。
