Transient receptor potential melastatin 2 regulates neutrophil extracellular traps formation and delays resolution of neutrophil-driven sterile inflammation

Journal of Inflammation

Research

Martin Herrmann¹  Tianshu Chu²  Yi Liu³  Yanhong Li³  Hang Yang³  Ji Wen³  Yubin Luo³  Yi Zhao⁴  Xue Cao⁵ 

[1] Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander- University Erlangen-Nürnberg (FAU), Erlangen, Germany;Department of Rheumatology and Immunology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, China;Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China;Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China;Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander- University Erlangen-Nürnberg (FAU), Erlangen, Germany;Department of Rheumatology & Immunology, West China Hospital, Sichuan University, No.37, Guoxue Alley, 610041, Chengdu, Sichuan, China;Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China;Department of Rheumatology and Immunology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, China;

关键词: TRPM2;    Neutrophil extracellular traps;    Sterile inflammation;    MSU crystals;    ROS;    NET formation;   

DOI  :  10.1186/s12950-023-00334-1

 received in 2022-11-11, accepted in 2023-02-10,  发布年份 2023

来源: Springer

【 摘 要 】

The formation of neutrophil extracellular traps (NETs) is a process releasing into the extracellular space networks of chromatin fibers decorated with granular proteins. It is implicated in infection-related as well as sterile inflammation. Monosodium urate (MSU) crystals serve as damage-associated molecular pattern (DAMP) in various conditions of disease. Formation of NETs or aggregated NETs (aggNETs) orchestrates initiation and resolution of MSU crystals-triggered inflammation, respectively. Elevated intracellular calcium levels and the generation of reactive oxygen species (ROS) are crucial for the formation of MSU crystal-induced NETs. However, the exact signaling pathways involved are still elusive. Herein, we demonstrate that the ROS-sensing, non-selective calcium-permeable channel transient receptor potential cation channel subfamily M member 2 (TRPM2) is required for a full-blown MSU crystal-induced NET formation. Primary neutrophils from TRPM2−/− mice showed reduced calcium influx and ROS production and, consequently a reduced formation of MSU crystal-induced NETs and aggNETs. Furthermore, in TRPM2−/− mice the infiltration of inflammatory cells into infected tissues and their production of inflammatory mediators was suppressed. Taken together these results describe an inflammatory role of TRPM2 for neutrophil-driven inflammation and identify TRPM2 as potential target for therapeutic intervention.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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