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Updated: Jan 29, 2026

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Transcriptomic Analysis Reveals Novel Mechanisms Underlying Neutrophil Activation Induced by High Salt.

Ignacio Mazzitelli1, Lucía Bleichmar1, Federico Rivelli1

  • 1Facultad de Medicina, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires, CONICET, Buenos Aires C1121ABG, Argentina.

International Journal of Molecular Sciences
|January 28, 2026
PubMed
Summary

High salt concentrations significantly alter neutrophil gene expression, activating immune responses through specific molecular pathways. This salt-induced neutrophil plasticity suggests roles beyond innate immunity.

Keywords:
inflammationmitochondrial ROSneutrophilssodium chloride

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Elevated sodium levels are common in tumors and inflamed tissues.
  • High salt concentrations are known to affect T cells and macrophages.
  • Neutrophils, key immune cells, have not been fully characterized in high-salt environments.

Purpose of the Study:

  • To investigate the impact of high salt concentrations on neutrophil gene expression and function.
  • To elucidate the molecular mechanisms underlying salt-induced neutrophil activation.
  • To explore the potential for neutrophils to adopt new functions under high-salt conditions.

Main Methods:

  • Transcriptomic analysis of neutrophils exposed to high salt.
  • Functional assays to assess neutrophil activation.
  • Integration of transcriptomic data with functional outcomes.

Main Results:

  • High salt exposure caused profound changes in the neutrophil transcriptome, exceeding responses to conventional agonists.
  • Salt-induced neutrophil activation involves mitochondrial reactive oxygen species (ROS) production.
  • Activation pathways include p38 MAPK, FOS, Bruton's tyrosine kinase (BTK), and cyclooxygenase 2 (COX2).
  • Neutrophils upregulated genes typically found in other cell types (e.g., SEMG1, ICAM4, TRIM69, AREG, OSM, TOB1).

Conclusions:

  • High salt concentrations induce significant transcriptomic plasticity in neutrophils.
  • Neutrophil activation by high salt involves ROS, p38 MAPK, FOS, BTK, and COX2 pathways.
  • Neutrophils may possess functions beyond innate immunity, influenced by the tumor microenvironment's salt levels.