Macrophage polarization refers to the process by which macrophages can produce two distinct functional phenotypes: M1 or M2. The balance between both strongly affects the progression of inflammatory disorders. Here, we review how redox signals regulate macrophage polarization and reprogramming during acute inflammation. In M1, macrophages augment NADPH oxidase isoform 2 (NOX2), inducible nitric oxide synthase (iNOS), synaptotagmin-binding cytoplasmic RNA interacting protein (SYNCRIP), and tumor necrosis factor receptor-associated factor 6 increase oxygen and nitrogen reactive species, which triggers inflammatory response, phagocytosis, and cytotoxicity. In M2, macrophages down-regulate NOX2, iNOS, SYNCRIP, and/or up-regulate arginase and superoxide dismutase type 1, counteract oxidative and nitrosative stress, and favor anti-inflammatory and tissue repair responses. M1 and M2 macrophages exhibit different metabolic profiles, which are tightly regulated by redox mechanisms. Oxidative and nitrosative stress sustain the M1 phenotype by activating glycolysis and lipid biosynthesis, but by inhibiting tricarboxylic acid cycle and oxidative phosphorylation. This metabolic profile is reversed in M2 macrophages because of changes in the redox state. Therefore, new therapies based on redox mechanisms have emerged to treat acute inflammation with positive results, which highlights the relevance of redox signaling as a master regulator of macrophage reprogramming.
Keywords: inflammation; macrophage polarization; oxidative stress; redox signaling.