[Resistance to acute hypoxia and changes in the phenotype and phenotypic plasticity of macrophages in mice of different genetic strains]

The aim of study was to investigate the effect of hypoxia on the macrophage phenotype and phenotypic plasticity and to determine the resistance to acute hypoxia in C57/BL mice, which have the pro-inflammatory M1 macrophage phenotype, and in BALB/c mice, which have the anti-inflammatory M2 macrophage phenotype. The following results were obtained. 1) The response of macrophages to acute hypoxia has two successive phases, the immediate, anti-inflammatory phase, and the delayed, pro-inflammatory phase. This response was more distinctly inverted in C57/BL6 M1 macrophages than in BALB/c M2 macrophages; 2) the effect of acute hypoxia on macrophage phenotypic plasticity depends on the genetically predetermined, original macrophage phenotype. In this process, a clear regularity was observed: hypoxia increased the capability of macrophages for changing into the pro-inflammatory M1 phenotype, while their capability for changing into the anti-inflammatory M2 phenotype remained virtually unaffected. 3) BALB/c mice were more resistant to acute hypoxia than C57/BL6 mice. Taken together, these data expand our understanding of mechanisms for pathogenetic effects of hypoxia.