Influence of low oxygen tensions on macrophage polarization.

Microenvironmental conditions in infected, inflamed or damaged tissues are characterized by low levels of oxygen (hypoxia) and nutrients. Myeloid cells (mostly macrophages and neutrophils) account for 95% of the cells newly recruited into inflammatory sites, and exert their effector functions under these restrictive conditions. In the case of macrophages, adaptation to the surrounding tissue environment is underlined by their huge metabolic and functional plasticity, which allows them to critically participate in the maintenance of tissue homeostasis and the initiation and resolution of inflammatory processes under hypoxic conditions. Therefore, alterations in oxygen availability directly affect the macrophage functional state (polarization), a phenomenon that has been already illustrated in pathologies like cancer, atherosclerosis and obesity. This review summarizes recent advances on the molecular basis of macrophage sensing and response to changes in oxygen pressure, emphasizing the link among the hypoxia-induced signalling pathways, macrophage polarization and inflammatory pathologies.