Suppression of neutrophils by sodium exacerbates oxidative stress and arthritis

Front Immunol. 2023 Aug 2:14:1174537. doi: 10.3389/fimmu.2023.1174537. eCollection 2023.

Abstract

Introduction: 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.

Methods: We investigated the effect of sodium chloride (NaCl) on neutrophil viability and functions in vitro, and in vivo employing the murine K/BxN-serum transfer arthritis (STA) model.

Results and discussion: The effects of NaCl and external reactive oxygen species (H2O2) were further examined on osteoclasts in vitro. 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 H2O2 addition to isotonic media. In contrast to NaCl, external H2O2 had pro-resorptive effects in vitro. 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.

Keywords: K/BxN serum transfer arthritis; neutrophil extracellular traps (NETs); neutrophils; osteoclasts; reactive oxygen species; sodium chloride.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis*
  • Hydrogen Peroxide
  • Mice
  • Neutrophils
  • Oxidative Stress
  • Reactive Oxygen Species
  • Sodium Chloride / pharmacology
  • Sodium Chloride, Dietary
  • Sodium*

Substances

  • Sodium
  • Sodium Chloride
  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • Sodium Chloride, Dietary

Grants and funding

This work was partially supported by the Deutsche Forschungsgemeinschaft (DFG) 2886 PANDORA Project-No. B3 to MH and JT; Project-No. TP04 to US; CRC1181- 261193037 (C03) to MH; SFB/TRR 241 (B04) to MH; by the European Union H2020-FETOPEN-2018-2019-2020-01 to MH; by the European Commission 861878, “NeutroCure”; to MH; by the Volkswagen-Stiftung (Grant 97744) to MH and RB; by the National Research Foundation of Ukraine grant 2020.02.0131 to RB; ERC Synergy grant 810316 4D NanoSCOPE to US, EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking RTCure grant no. 777357 to US, ELAN Fond of the Friedrich-Alexander-Universität Erlangen-Nürnberg (P097) to US; DFG MU 4240/2-1 (Project Nr. 470134687) and International Collaborative Project of Science & Technology Department of Sichuan Province (2022YFH0023) to LM. We acknowledge financial support by Deutsche Forschungsgemeinschaft and Friedrich-Alexander-Universität Erlangen-Nürnberg within the funding programme “Open Access Publication Funding”.