metabolic-characterization-polarized-m1-m2-bone-marrow-derived

Metabolic Characterization of Polarized M1 and M2 Bone Marrow-derived Macrophages Using Real-time Extracellular Flux Analysis

Specific metabolic pathways are increasingly being recognized as critical hallmarks of macrophage subsets. While LPS-induced classically activated M1 or ...

Academic Medical Center, Amsterdam

Epigenetic enzymes are emerging as crucial controllers of macrophages, innate immune cells that determine the outcome of many inflammatory diseases. Recent studies demonstrate that the activity of particular chromatin-modifying enzymes is regulated by the availability of specific metabolites like acetyl-coenzyme A, S-adenosylmethionine, α-ketoglutarate, nicotinamide adenine dinucleotide and polyamines. In this way chromatin-modifying enzymes could sense the macrophage's metabolic status and translate this into gene expression and phenotypic changes. Importantly, distinct macrophage activation subsets display particular metabolic pathways. IFNγ/lipopolysaccharide-activated macrophages (MIFNγ/LPS or M1) display high glycolysis, which directly drives their inflammatory phenotype. In contrast, oxidative mitochondrial metabolism and enhanced polyamine production are hallmarks and requirements for IL-4-induced macrophage activation (MIL-4 or M2). Here we report how epigenetics could serve as a bridge between altered macrophage metabolism, macrophage activation and disease.

Jeroen Baardman

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