Effect of acute hypoxia on phenotype and plasticity of M1 and M2 macrophages

Abstract

Federation Pathogenetic roles of hypoxia may be related with influences on immunity. The aim of study was to investigate the effect of hypoxia on the macrophage phenotype and plasticity in C57/BL mice, which have the pro‐inflammatory M1 macrophage phenotype, and in BALB/c mice, which have the anti‐inflammatory M2 one.MethodsHypoxia was produced in an altitude chamber. After hypoxia, macrophages were isolated from peritoneal lavage. NO production, inducible NO synthase content and cell shape were used as phenotype markers. To determine the phenotypic plasticity, we quantified the capability of macrophages for changing the phenotype to M1 and to M2.Results1) The response of macrophages to hypoxia has two successive phases, the immediate, anti‐inflammatory phase, and the delayed, pro‐inflammatory phase. These phases were more pronounced in Ñ57/BL6 M1 macrophages than in ÂÀLB/c M2 macrophages; 2) the effect of hypoxia on macrophage phenotypic plasticity depends on the genetically predetermined macrophage phenotype. Hypoxia increased the capability of macrophages for changing to the pro‐inflammatory M1 phenotype, while their capability for changing to the anti‐inflammatory M2 phenotype remained virtually unaffected.ConclusionEffects of hypoxia involve immune responses and depend on the genetically predetermined macrophage phenotype. This study was supported by the RFBR (12–04‐01191‐a)