More than just protein building blocks: how amino acids and related metabolic pathways fuel macrophage polarization.
More than just protein building blocks: how amino acids and related metabolic pathways fuel macrophage polarization.
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不仅仅是蛋白质构建模块：氨基酸及相关代谢途径如何促进巨噬细胞极化
DOI：
10.1111/febs.15715
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Schabbauer G
中科院分区：
文献类型：
--
作者：
Kieler M;Hofmann M;Schabbauer G
巨噬细胞是先天免疫反应的第一道防线，并且在调节宿主炎症和组织内稳态方面还具有重要作用。M1/M2模型描述了巨噬细胞极化状态的两个极端，它们可由多种刺激诱导，最显著的是由脂多糖/干扰素 -γ和白细胞介素 -4/白细胞介素 -13诱导。从历史上看，编码两种以相同氨基酸为底物的酶（诱导型一氧化氮合酶和精氨酸酶1）的两个基因的表达，一直被用于定义经典激活的M1（诱导型一氧化氮合酶）和替代激活的M2（精氨酸酶1）巨噬细胞。这种“精氨酸二分法”最近成为了一个有争议的问题；然而，随着免疫代谢这一新兴领域的出现，越来越多的证据表明这两种酶及其相关代谢产物从根本上参与了巨噬细胞极化和功能的内在调节。本综述的目的是强调巨噬细胞生物学和免疫代谢的最新进展，特别关注氨基酸代谢及其相关代谢途径：诱导型一氧化氮合酶/精氨酸酶1（精氨酸）、三羧酸循环和氧化磷酸化（谷氨酰胺）以及一碳代谢（丝氨酸、甘氨酸）。
巨噬细胞是先天免疫的关键参与者，对多种促炎和抗炎刺激作出反应，导致极化状态呈现连续变化。M1/M2模型描述了这一谱系的两个极端。新出现的证据表明代谢在免疫生物学中起关键作用，并强调了特定氨基酸及其相关代谢途径在巨噬细胞极化中的重要性。
Macrophages represent the first line of defence in innate immune responses and additionally serve important functions for the regulation of host inflammation and tissue homeostasis. The M1/M2 model describes the two extremes of macrophage polarization states, which can be induced by multiple stimuli, most notably by LPS/IFN‐γ and IL‐4/IL‐13. Historically, the expression of two genes encoding for enzymes, which use the same amino acid as their substrate, iNOS and ARG1, has been used to define classically activated M1 (iNOS) and alternatively activated M2 (ARG1) macrophages. This ‘arginine dichotomy’ has recently become a matter of debate; however, in parallel with the emerging field of immunometabolism there is accumulating evidence that these two enzymes and their related metabolites are fundamentally involved in the intrinsic regulation of macrophage polarization and function. The aim of this review is to highlight recent advances in macrophage biology and immunometabolism with a specific focus on amino acid metabolism and their related metabolic pathways: iNOS/ARG1 (arginine), TCA cycle and OXPHOS (glutamine) as well as the one‐carbon metabolism (serine, glycine). Macrophages are key players in innate immunity and react to a great variety of pro‐ and anti‐inflammatory stimuli, which result in a continuum of polarization states. The M1/M2 model describes the two extremes of this spectrum. Emerging evidence points towards a key role of metabolism in immunobiology and highlights the importance of specific amino acids and their related metabolic pathways in macrophage polarization.
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影响因子：
37.8
作者：
Cheng S;Rhee EP;Larson MG;Lewis GD;McCabe EL;Shen D;Palma MJ;Roberts LD;Dejam A;Souza AL;Deik AA;Magnusson M;Fox CS;O'Donnell CJ;Vasan RS;Melander O;Clish CB;Gerszten RE;Wang TJ
通讯作者：
Wang TJ
影响因子：
16.6
作者：
Davies LC;Rice CM;Palmieri EM;Taylor PR;Kuhns DB;McVicar DW
通讯作者：
McVicar DW
影响因子：
16.6
作者：
Brunner, Julia S.;Vulliard, Loan;Schabbauer, Gernot
通讯作者：
Schabbauer, Gernot
DOI：
10.1016/0304-4165(76)90005-2
发表时间：
1976-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
CULVENOR, JG;WEIDEMANN, MJ
通讯作者：
WEIDEMANN, MJ
影响因子：
6.7
作者：
Esser-von Bieren J;Mosconi I;Guiet R;Piersgilli A;Volpe B;Chen F;Gause WC;Seitz A;Verbeek JS;Harris NL
通讯作者：
Harris NL