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Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Typical Western diet, rich in salt, contributes to autoimmune disease development. However, conflicting reports exist about the effect of salt on neutrophil effector functions, also in the context of arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the effect of sodium chloride (NaCl) on neutrophil viability and functions <jats:italic>in vitro<\/jats:italic>, and <jats:italic>in vivo<\/jats:italic> employing the murine K\/BxN-serum transfer arthritis (STA) model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>The effects of NaCl and external reactive oxygen species (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) were further examined on osteoclasts <jats:italic>in vitro.<\/jats:italic> Hypertonic sodium-rich media caused primary\/secondary cell necrosis, altered the nuclear morphology, inhibited phagocytosis, degranulation, myeloperoxidase (MPO) peroxidation activity and neutrophil extracellular trap (NET) formation, while increasing total ROS production, mitochondrial ROS production, and neutrophil elastase (NE) activity. High salt diet (HSD) aggravated arthritis by increasing inflammation, bone erosion, and osteoclast differentiation, accompanied by increased NE expression and activity. Osteoclast differentiation was decreased with 25 mM NaCl or 100 nM H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> addition to isotonic media. In contrast to NaCl, external H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> had pro-resorptive effects <jats:italic>in vitro<\/jats:italic>. We postulate that in arthritis under HSD, increased bone erosion can be attributed to an enhanced oxidative milieu maintained by infiltrating neutrophils, rather than a direct effect of NaCl.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1174537","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T12:40:40Z","timestamp":1690980040000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Suppression of neutrophils by sodium exacerbates oxidative stress and 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