Fig. 8.
Depletion of nitric oxide and increasing antioxidant gene expression supports polarisation to M2 macrophages. As macrophages encounter apoptotic cells that have exposed oxidised phosphatidyl serine on the outer membrane leaflet, downstream increases in PPARγ and AMPK activity are induced. Downstream of AMPK activation, an increase in NAD+ promotes SIRT1 activation deacetylation of mitochondrial genes, increases their expression and so increases oxidative phosphorylation potential. In parallel, the increase in PPARγ causes an increase in arginase expression. Arginase consumes the substrate for iNOS, arginine, hence NO production becomes limited. In concert, AMPK and PPARγ enhance the activity of PGC1α with a resulting increase in mitochondrial SOD expression. The latter protects mitochondrial membrane components from risk of oxidative damage by O2-. removal. Citric acid enzyme expression is also increased such that the substrates for oxidative phosphorylation, reduced nucleotides, are increased in concentration and support ATP production.