Environmental oxygen tension affects phenotype in cultured bone marrow-derived macrophages

This study tested the hypothesis that the unique phenotype of alveolar macrophages (AM) is maintained through adaptation to the relatively high oxygen partial pressure (Po-2) of the lung, through modification of redox-sensitive transcription factors. BALB/c mouse bone marrow-derived macrophages (BMC) were differentiated under different Po-2 and compared functionally to AM and peritoneal macrophages ( PM). BMC differentiated in normoxia (Po-2 140 Torr, BMChigh) were similar to AM in having low phagocytic and antigen presenting cell (APC) activities. However, BMC grown in low oxygen tension as found in other tissues ( < 40 Torr, BMClow) were better phagocytes and APCs, similar to PM. BMChigh were more oxidative intracellularly than BMClow, based on oxidation of dichlorofluorescein and higher glutathione disulfide/glutathione (GSH) ratios, despite having more GSH. Finally, lipopolysaccharide-induced nuclear factor-κB translocation, measured by laser scanning cytometry, was reduced in BMChigh and AM, compared with BMClow and PM, respectively. These data suggest that regulation of the AM phenotype may occur, at least in part, via inhibition of NF-κB by the unique redox environment.