Sodium bicarbonate regulates nitric oxide production in mouse macrophage cell lines stimulated with lipopolysaccharide and interferon γ

Macrophages are known to play pivotal roles in host-defense through inflammation via both innate and acquired immune systems, and so on. In an earlier paper, we showed the influence of the type of culture medium, Ham's F-12 or DMEM, on activated macrophage phenotypes induced by LPS and IFN gamma. The production of nitric oxide (NO), pro-inflammatory cytokines such as TNF alpha and IL-1 beta, as well as the induction of superoxide-generating activity of J774.1/JA-4 cells was different depending on the type of culture medium. In this present study, we showed that sodium bicarbonate concentrations in these culture media, 14 mM in Ham's F-12 and 44 mM in DMEM, were crucial to explaining the differences in the induction of activated macrophage phenotypes, especially in that of iNOS. A concentration-dependent change in pH did not result in any remarkable difference in iNOS expression or NO production. Moreover, high sodium bicarbonate in culture medium increased not only NO production but also TNF alpha production in the activated macrophages. These results suggest that sodium bicarbonate would be a regulatory factor of NO and TNF alpha production in macrophages and that its concentration has a crucial role in macrophage activation.