More than just protein building blocks: how amino acids and related metabolic pathways fuel macrophage polarization. (22nd February 2021)

• Record Type: Journal Article
• Authors: Kieler, Markus; Hofmann, Melanie; Schabbauer, Gernot
• Is Part Of: FEBS journal. Volume 288:Number 12(2021)
• Page Start: 3694
• Page End: 3714
• Publication Date: 2021-02-22
• Subjects: arginase/iNOS -- glutamine -- immunometabolism -- macrophage polarization -- nitric oxide -- oxidative phosphorylation -- polyamines -- serine -- TCA cycle -- α‐ketoglutarate; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.15715
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : 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). Abstract : 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.