Table 1.

The characteristics of M1-like versus M2-like macrophages

	M1-like macrophages	M2-like macrophages
Inducers	IFN-γ, TNF-α, TLR ligands, bacterial products (such as LPS)	IL-4, IL-10, IL-13, TGF-β, CSF1, PGE2, glucocorticoids
Phenotypic markers	HLA-DR, CD80, CD86	CD163, CD204, CD206
Secreted/produced molecules	IL-1α, IL-1β, IL-6, IL-12, IL-23, TNF-α, iNOS, ROS	IL-10, TGF-β, PGE2, VEGF, MMPs, ARG1
Metabolism	Highly glycolytic—dependent on the stabilization of HIF-1α; increased generation of lactic acid	Glycolysis is dispensable when OXPHOS is intact
	↑PPP flux → ↑NADPH production → generation of NO and ROS; lipid biosynthesis	↓PPP flux
	↑lipid synthesis → membrane biogenesis, granule formation	↑FAO
	Impaired TCA cycle → accumulation of citrate and succinate → fatty acid synthesis and generation of inflammatory effector molecules—for example, NO	Intact TCA cycle driven by FAO and glutamine catabolism
	Impaired OXPHOS and ETC → ↑ROS generation	↑OXPHOS and mitochondrial biogenesis
	↑iNOS expression → arginine is preferentially catabolized into NO	↑ARG1 expression → arginine is preferentially catabolized into ornithine and urea → production of polyamines and proline → cell growth and collagen synthesis
Functions	Proinflammatory, pathogen clearance, antitumor properties	Anti-inflammatory, tissue repair and remodeling, protumorigenic properties—immunosuppression, angiogenesis, tumor cell invasion and metastasis

CSF1, colony-stimulating factor 1; ETC, electron transport chain; FAO, fatty acid oxidation; HIF-1α, hypoxia-inducible factor 1α; HLA-DR, human leukocyte antigen-DR; IFN, interferon; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; MMP, matrix metalloproteinase; NADPH, nicotinamide adenine dinucleotide phosphate; NO, nitric oxide; OXPHOS, oxidative phosphorylation; PGE2, prostaglandin E2; PPP, pentose phosphate pathway; ROS, reactive oxygen species; TCA cycle, tricarboxylic acid cycle; TLR, toll-like receptor; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.