High Salt Induces a Delayed Activation of Human Neutrophils

Mazzitelli, Ignacio; Bleichmar, Lucía; Melucci, Claudia; Gerber, Pehuén Pereyra; Toscanini, María A.; Cuestas, María Luján; Díaz, Fernando Erra; Geffner, Jorge

doi:10.3389/fimmu.2022.831844

Cited by 10 publications

(7 citation statements)

References 47 publications

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“…In our settings, neutrophils were simultaneously activated by PMA/Pyocyanin and treated with high salt; these conditions augmented ROS production in high hypertonicity. This is in line with recent findings where NaCl initially inhibits (up to 2 hours) ( 18 , 40 ) but later (6 to 18 hours) fosters ROS production ( 18 ), even at lower osmolarities (190 - 200 mM). Our higher salinity was enough to induce oxidative stress in short-term cell cultures.…”

Section: Discussionsupporting

confidence: 93%

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Suppression of neutrophils by sodium exacerbates oxidative stress and arthritis

Zlatar,

Mahajan,

Muñoz-Becerra

et al. 2023

Front. Immunol.

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IntroductionTypical 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.MethodsWe 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 discussionThe 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.

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Section: Discussionsupporting

confidence: 93%

“…The latest publication showed that the effect of additional 50 mM NaCl was time-dependent and caused a delayed activation of human neutrophils. In short-term and long-term neutrophil cultures, production of IL-8 and respiratory burst were inhibited or augmented, respectively ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Suppression of neutrophils by sodium exacerbates oxidative stress and arthritis

Zlatar,

Mahajan,

Muñoz-Becerra

et al. 2023

Front. Immunol.

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“…Furthermore, a recent study by Hishida et al demonstrated that IL-1ß deficiency attenuated the methylglyoxal-induced PF [ 28 ]. Similarly to our results, Mazzitelli et al found that while high-salt environment leads to the activation of neutrophils, osmotic control mannitol had no effect [ 29 ]. This phenomenon may be because immune cells express a high number of sodium transport proteins that can activate inflammatory pathways in lymphocytes independently from osmotic stress [ 30 ].…”

Section: Discussionsupporting

confidence: 91%

High Salt Promotes Inflammatory and Fibrotic Response in Peritoneal Cells

Pap,

Pajtók,

Veres-Székely

et al. 2023

IJMS

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Recent studies draw attention to how excessive salt (NaCl) intake induces fibrotic alterations in the peritoneum through sodium accumulation and osmotic events. The aim of our study was to better understand the underlying mechanisms. The effects of additional NaCl were investigated on human primary mesothelial cells (HPMC), human primary peritoneal fibroblasts (HPF), endothelial cells (HUVEC), immune cells (PBMC), as well as ex vivo on peritoneal tissue samples. Our results showed that a high-salt environment and the consequently increased osmolarity increase the production of inflammatory cytokines, profibrotic growth factors, and components of the renin–angiotensin–aldosterone system, including IL1B, IL6, MCP1, TGFB1, PDGFB, CTGF, Renin and Ace both in vitro and ex vivo. We also demonstrated that high salt induces mesenchymal transition by decreasing the expression of epithelial marker CDH1 and increasing the expression of mesenchymal marker ACTA2 and SNAIL1 in HPMCs, HUVECs and peritoneal samples. Furthermore, high salt increased extracellular matrix production in HPFs. We demonstrated that excess Na+ and the consequently increased osmolarity induce a comprehensive profibrotic response in the peritoneal cells, thereby facilitating the development of peritoneal fibrosis.

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“…However, a recent study by M azzitelli et al . [ 34 ] found the opposite, concluding that high salt concentration, rather than osmolarity, led to activation of the neutrophil response. Regardless of the mechanism, it can be speculated that ATP hydrolysis in ciliated epithelial cells may also be affected by HS and reduce CBF.…”

Section: Discussionmentioning

confidence: 99%

Impact of high- and low-flow nebulised saline on airway hydration and mucociliary transport

Kelly

Valentine²,

Chua³

et al. 2023

ERJ Open Res

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Nebulized drugs, including osmotic agents and saline, are increasingly used during non-invasive respiratory support including nasal high-flow therapy. The authors conducted anin vitrostudy to compare the hydration effect of nebulized isotonic 0.9% and hypertonic 7.0% saline on mucociliary transport.In a perfused organ bath, 10 sheep tracheas were exposed to 7.5 mL nebulized 0.9% and 7.0% saline entrained into heated (38 °C) and humidified air delivered at high- and low-flow (20 and 7 L·min−1, respectively). Simultaneous measurements of the airway surface liquid height, mucus transport velocity, cilia beat frequency and surface temperature were made over time. The data was presented as mean±sd.The airway surface liquid height increased significantly with both 0.9% and 7.0% saline: at low-flow by 37.2±10.0 µm and 152.7±10.9 µm, and at high-flow by 62.3±5.6 µm and 163.4±25.4 µm (p<0.001), respectively. Mucus velocity was increased by both 0.9% and 7.0% saline from a baseline of 8.2±0.8 mm·min−1to 8.8±0.7 mm·min−1and 17.1±0.5 mm·min−1with low-flow and at high-flow to 9.8±0.02 mm·min−1(p=0.04) and 16.9±0.5 mm·min−1(p<0.05), respectively. Ciliary beating did not change with 0.9% saline but declined from 13.1±0.6 Hz to 10.2±0.6 Hz and 11.1±0.6 Hz (p<0.05) with 7.0% saline at low- and high-flow, respectively.The findings demonstrate that nebulized isotonic 0.9% saline like hypertonic 7.0% saline significantly stimulates basal mucociliary transport and the use of high-flow delivery had no significantly different hydration effects compared with low-flow. Hypertonic 7.0% saline suppressed ciliary beating indicating an increase in airway surface liquid osmolarity, which may have negative effects on the airway surface with frequent use.

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High Salt Induces a Delayed Activation of Human Neutrophils

Cited by 10 publications

References 47 publications

Suppression of neutrophils by sodium exacerbates oxidative stress and arthritis

Suppression of neutrophils by sodium exacerbates oxidative stress and arthritis

High Salt Promotes Inflammatory and Fibrotic Response in Peritoneal Cells

Impact of high- and low-flow nebulised saline on airway hydration and mucociliary transport

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