Suppression of neutrophils by sodium exacerbates oxidative stress and arthritis

Leticija Zlatar, Aparna Mahajan, Marco Muñoz-Becerra, Daniela Weidner, Galyna Bila, Rostyslav Bilyy, Jens Titze, Markus H. Hoffmann, Georg Schett, Martin Herrmann, Ulrike Steffen, Luis E. Muñoz*, Jasmin Knopf

*Corresponding author for this work

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.

Original languageEnglish
Article number1174537
JournalFrontiers in Immunology
Volume14
Pages (from-to)1174537
ISSN1664-3224
DOIs
Publication statusPublished - 2023

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Centers: Center for Research on Inflammation of the Skin (CRIS)

DFG Research Classification Scheme

  • 204-05 Immunology

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