Figure 2.

Macrophage polarization. Monocytes are recruited to the site of injury and therein undergo a process of differentiation into M1 (classically-activated) or M2 (alternatively activated) species depending on the microenvironmental cues encountered. The M1 phenotype is induced by immunostimulant molecules such as IFN-γ and bacterial LPS, while the M2 phenotype is induced following exposure to cytokines such as IL-10, IL-13, and TGF-β. M1 macrophage activation and expression of MHC class II antigens propagate further inflammatory signaling and cytokine release, which, despite promoting pathogen killing and immunity, may eventually lead to injury site fibrosis and scarring. M2 macrophages are generally thought to attenuating organ injury by suppressing inflammation and promoting beneficial matrix remodeling and repair, partially via their release of regenerative and anti-inflammatory factors such as IL-10.⁹⁹ GC, glucocorticoids; IFN, interferon; LPS, lipopolysaccharide; MHC, major histocompatibility class; NO, nitric oxide; ROS, reactive oxygen species; TGF, transforming growth factor; TNF, tumor necrosis factor.