Schematic representation of M? polarization. While M1/classically activated macrophages are typically induced by IFNγ and microbial products like LPS, different stimuli lead to the development of an array of finely tuned alternately activated states. IC, Immune complex; HH, Hapto-hemoglobin; OxRBC, oxidized red blood cells; Ox-PL-PPC, ox-PL 1-palmitoyl-2arachidonoyl-sn-glycero-3-phosphorycholine; FFA, free fatty acid.|@|~(^,^)~|@|Major signaling pathways involved in M1/M2 M? polarization. STAT1/3 and STAT6 regulate transcription of M1 and M2 genes following recognition of IFNγ or IL-4/13 by their surface receptors and activation of JAKs (A). Differential activation of Akt1 or Akt2 via PI3K and PIP3 leads to either M2 or M1 polarization, respecively (B). Upon activation, the intracellular domain of Notch (NICD) is cleaved and activates IRF8 to promote M1 polarization. GM-CSF triggers M1 polarization via IRF5 while M-CSF induces M2 polarization via IRF4 (C).

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