Macrophage polarization in hypoxia and ischemia/reperfusion: Insights into the role of energetic metabolism

Macrophages, the key cells of innate immunity, possess wide phenotypical and functional heterogeneity. In vitro studies showed that microenvironment signals could induce the so-called polarization of macrophages into two phenotypes: classically activated macrophages (M1) or alternatively activated macrophages (M2). Functionally, they are considered as proinflammatory and anti-inflammatory/pro-regenerative, respectively. However, in vivo studies into macrophage states revealed a continuum of phenotypes from M1 to M2 state instead of the clearly distinguished extreme phenotypes. An important role in determining the type of polarization of macrophages is played by energy metabolism, including the activity of oxidative phosphorylation. In this regard, hypoxia and ischemia that affect cellular energetics can modulate macrophage polarization. Here, we overview the data on macrophage polarization during metabolic shift-associated pathologies including ischemia and ischemia/reperfusion in various organs and discuss the role of energy metabolism potentially triggering the macrophage polarization.

Automated summary

Macrophages, the key cells of innate immunity, exhibit wide phenotypical and functional heterogeneity. They can polarize into classically activated (M1) or alternatively activated (M2) phenotypes in response to microenvironment signals. However, in vivo studies have shown a continuum of phenotypes from M1 to M2, rather than distinct extreme phenotypes. Energy metabolism, including oxidative phosphorylation, plays a crucial role in determining macrophage polarization.