Polarization and repolarization of macrophages

Macrophages can acquire distinct phenotypes and biological functions depending on the microenvironment and the metabolic state. Macrophages classically activated by IFN-γ and/or microbial products display an M1 phenotype characterized by high expression of interleukin (IL)-12, inducible nitric oxide synthase (iNOS) and TNF-α. They trigger a Th1 immune response and are generally considered potent effector cells which kill microorganisms and tumor cells. Alternatively activated or M2 macrophages are stimulated by IL-4, IL-10, IL-13, immune complexes, or glucocorticoids. M2 phenotype is characterized by low iNOS and IL-12 production and triggers Th2 response. M2 macrophages are involved in tissue repair and angiogenesis. M1 and M2 macrophages display differences in metabolism and reduced glutathione (GSH) concentration. This review describes the main macrophage phenotypes with a major focus on the differences in protein, glucose and lipid metabolism. Moreover, repolarization of macrophages as potential therapeutic approach and the critical role of GSH in regulating repolarization are discussed.