Hyponatremia unleashes neutrophil extracellular traps elevating life- threatening pulmonary embolism risk

• 成果类型: Article
• 署名作者: Inoue, Minoru; Takayama, Kazuo; Hashimoto, Rina; Enomoto, Masahiro; Date, Naoki; Ohsumi, Akihiro; Mizowaki, Takashi
• 署名单位: Kyoto University; Kyoto University; Shizuoka Cancer Center; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; Kyoto University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10423
• DOI: 10.1073/pnas.2404947121
• 发表日期: 2024-11-05
• 关键词: congestive-heart-failure; sodium-calcium exchange; prognostic value; cell-death; dna traps; mortality; promote; netosis; activation; contribute

摘要

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 (ROS), 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 insights into the pathogenesis of hyponatremia- associated diseases, highlighting potential therapeutic interventions targeting NETs dynamics.