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Fish Macrophages Show Distinct Metabolic Signatures Upon Polarization.
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2020-01-21 , DOI: 10.3389/fimmu.2020.00152
Annelieke S Wentzel 1 , Joëlle J E Janssen 1, 2 , Vincent C J de Boer 2 , Wouter G van Veen 3 , Maria Forlenza 1 , Geert F Wiegertjes 4
Affiliation  

Macrophages play important roles in conditions ranging from host immune defense to tissue regeneration and polarize their functional phenotype accordingly. Next to differences in the use of L-arginine and the production of different cytokines, inflammatory M1 macrophages and anti-inflammatory M2 macrophages are also metabolically distinct. In mammals, M1 macrophages show metabolic reprogramming toward glycolysis, while M2 macrophages rely on oxidative phosphorylation to generate energy. The presence of polarized functional immune phenotypes conserved from mammals to fish led us to hypothesize that a similar metabolic reprogramming in polarized macrophages exists in carp. We studied mitochondrial function of M1 and M2 carp macrophages under basal and stressed conditions to determine oxidative capacity by real-time measurements of oxygen consumption and glycolytic capacity by measuring lactate-based acidification. In M1 macrophages, we found increased nitric oxide production and irg1 expression in addition to altered oxidative phosphorylation and glycolysis. In M2 macrophages, we found increased arginase activity, and both oxidative phosphorylation and glycolysis were similar to control macrophages. These results indicate that M1 and M2 carp macrophages show distinct metabolic signatures and indicate that metabolic reprogramming may occur in carp M1 macrophages. This immunometabolic reprogramming likely supports the inflammatory phenotype of polarized macrophages in teleost fish such as carp, similar to what has been shown in mammals.



中文翻译:

鱼巨噬细胞在极化时显示不同的代谢特征。

巨噬细胞在从宿主免疫防御到组织再生的各种条件下发挥重要作用,并相应地极化其功能表型。除了在使用L-精氨酸和产生不同细胞因子方面的差异外,炎症性M1巨噬细胞和抗炎性M2巨噬细胞在代谢上也很明显。在哺乳动物中,M1巨噬细胞显示代谢重编程为糖酵解,而M2巨噬细胞依靠氧化磷酸化产生能量。从哺乳动物到鱼类保守的极化功能性免疫表型的存在使我们假设鲤鱼中存在极化巨噬细胞中类似的代谢重编程。我们研究了在基础和应激条件下M1和M2鲤鱼巨噬细胞的线粒体功能,通过实时测量耗氧量和通过测量基于乳酸的酸化的糖酵解能力来确定氧化能力。在M1巨噬细胞中,我们发现一氧化氮的产生增加了,irg1除了改变氧化磷酸化和糖酵解的表达。在M2巨噬细胞中,我们发现精氨酸酶活性增加,并且氧化磷酸化和糖酵解均与对照巨噬细胞相似。这些结果表明,M1和M2鲤鱼巨噬细胞显示出独特的代谢特征,并表明可能在鲤鱼M1巨噬细胞中发生代谢重编程。这种免疫代谢的重编程可能支持硬骨鱼类(例如鲤鱼)中极化巨噬细胞的炎症表型,这与哺乳动物中所显示的相似。

更新日期:2020-02-26
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