Syntaxin-4 and SNAP23 are involved in neutrophil degranulation, but not in the release of mitochondrial DNA during NET formation

Frontiers in Immunology

Immunology

Kenneth R. McLeish¹  Lea Gigon²  Timothée Fettrelet²  Darko Stojkov²  Shida Yousefi²  Marta Miholic³  Hans-Uwe Simon⁴ 

[1] Department of Medicine, University of Louisville School of Medicine, Louisville, KY, United States;Institute of Pharmacology, University of Bern, Bern, Switzerland;Institute of Pharmacology, University of Bern, Bern, Switzerland;Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia;Institute of Pharmacology, University of Bern, Bern, Switzerland;Institute of Biochemistry, Brandenburg Medical School, Neuruppin, Germany;

关键词: degranulation;    EET;    eosinophils;    mitochondrial DNA;    NET;    neutrophils;    SNAP23;    syntaxin-4;   

DOI  :  10.3389/fimmu.2023.1272699

 received in 2023-08-04, accepted in 2023-09-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

Neutrophils are a specialized subset of white blood cells, which have the ability to store pre-formed mediators in their cytoplasmic granules. Neutrophils are well-known effector cells involved in host protection against pathogens through diverse mechanisms such as phagocytosis, degranulation, extracellular traps, and oxidative burst. In this study, we provide evidence highlighting the significance of the SNARE proteins syntaxin-4 and synaptosomal-associated protein (SNAP) 23 in the release of azurophilic granules, specific granules, and the production of reactive oxygen species in human neutrophils. In contrast, the specific blockade of either syntaxin-4 or SNAP23 did not prevent the release of mitochondrial dsDNA in the process of neutrophil extracellular trap (NET) formation. These findings imply that degranulation and the release of mitochondrial dsDNA involve at least partially distinct molecular pathways in neutrophils.

【 授权许可】

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Copyright © 2023 Gigon, Fettrelet, Miholic, McLeish, Yousefi, Stojkov and Simon