Hyponatremia unleashes neutrophil extracellular traps elevating life-threatening pulmonary embolism risk
Author:
Inoue Minoru1, Takayama Kazuo2ORCID, Hashimoto Rina2ORCID, Enomoto Masahiro3, Date Naoki4, Ohsumi Akihiro5ORCID, Mizowaki Takashi2ORCID
Affiliation:
1. Kyoto University Graduate School of Medicine 2. Kyoto University 3. Princess Margaret Cancer Centre, University Health Network, Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada 4. Kyoto University Hospital 5. University Health Network
Abstract
Abstract
Neutrophil extracellular traps (NETs), essential for controlling infections, can induce various pathologies when dysregulated. Known triggers for infection-independent NETs release exist, yet a comprehensive understanding of the conditions prompting such responses is lacking. In this study, we identify hyponatremia as an independent inducer of NETs release, a common clinical condition that disrupts sodium/calcium exchange within neutrophils. This disruption leads to an excess of intracellular calcium, subsequent elevation of reactive oxygen species, and the citrullination of histone H3, culminating in the activation of NETs-release pathways. Notably, under hyponatremic conditions, this mechanism is exacerbated during infectious states, leading to the deposition of NETs in the lungs and increasing the risk of life-threatening pulmonary embolism. Our findings underscore the critical role of sodium and calcium homeostasis in neutrophil functionality and provide novel insights into the pathogenesis of hyponatremia-associated diseases, highlighting potential therapeutic interventions targeting NETs dynamics.
Publisher
Research Square Platform LLC
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