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- W4313359557 abstract "Abstract Neutrophil extracellular trap (NET) formation represents an important antimicrobial function of neutrophils, which partly depends on reactive oxygen species (ROS) and autophagy activation. However, the factors governing these processes remain unknown. In this study, we demonstrate that nonselective calcium permeable cation channel Transient receptor potential melastatin 2 (TRPM2), senses ROS and contributes to the NET formation. The NET forming function of TRPM2 in response to ROS stimulation requires autophagy activation through ADP ribose, AMPK phosphorylation and p38 MAPK activation. TRPM2 deficient neutrophils fail to activate this pathway with a block of NET release and a concomitant impairment of antimicrobial capacity. Trpm2−/− mice were found to be highly susceptible to pneumonic infection with Klebsiella pneumoniae owing to an impaired NET formation and high bacterial burden despite increased neutrophil infiltration in their lungs. Taken together our data identifies a key role of TRPM2 in NET formation by ROS sensing and links it to autophagy activation via AMPK/p38 pathway. Our study also provides evidence for a protective anti-microbial role of TRPM2 in pneumonic bacterial infection thus positing TRPM2-mediated NET formation as a valuable target for modulating NETs and related pathologies." @default.
- W4313359557 created "2023-01-06" @default.
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- W4313359557 date "2018-05-01" @default.
- W4313359557 modified "2023-10-18" @default.
- W4313359557 title "Oxidant sensor cation channel TRPM2 activates neutrophil extracellular trap formation by autophagy and plays a protective role in pneumoseptic <i>Klebsiella pneumoniae</i> infection" @default.
- W4313359557 doi "https://doi.org/10.4049/jimmunol.200.supp.117.21" @default.
- W4313359557 hasPublicationYear "2018" @default.
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