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- W3035290143 abstract "Abstract Background Recent evidence demonstrates that activated eosinophils undergo a distinct form of lytic cell death, accompanied by formation of DNA‐based eosinophil extracellular trap (EET) and degranulation, enhancing inflammatory immune responses in asthmatic airways. We previously showed that human blood eosinophils undergo degranulation in response to lysophosphatidylserine (LysoPS), an inflammatory lipid mediator, and strongly express P2Y10, a LysoPS receptor. Methods We evaluated EET, degranulation, and cell death of eosinophils in response to various concentrations of LysoPS. We also compared responsiveness to LysoPS between eosinophils from severe and nonsevere asthmatics. Results Extensive EET formation was elicited from a substantial fraction of stimulated eosinophils in response to 50 μmol/L LysoPS. Analyses for LDH and eosinophil‐derived neurotoxin release showed that both lytic cell death and degranulation accompanied EET formation in response to LysoPS. Cytological analyses demonstrated that citrullinated histone 3 was present in the extracellular, filamentous DNA structure embedded with eosinophil granules. The LysoPS‐induced EET was independent of ROS production and irrelevant to several signaling pathways examined, but dependent on protein arginine deiminase 4. A low concentration of LysoPS (5 μmol/L) did not induce EET or degranulation, but significantly increased platelet‐activating factor‐induced degranulation. Eosinophils from severe asthmatics exhibited greater degranulation, but not EET formation, in response to LysoPS (50 μmol/L), than those from nonsevere asthmatics, along with great expression of surface P2Y10. Conclusions We identified a novel function of LysoPS, namely induction of EET in association with cytolysis and degranulation. LysoPS‐dependent EET or degranulation plays a potential role in eosinophilic inflammation of severe asthma." @default.
- W3035290143 created "2020-06-19" @default.
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- W3035290143 date "2020-07-10" @default.
- W3035290143 modified "2023-10-10" @default.
- W3035290143 title "Lysophosphatidylserine induces eosinophil extracellular trap formation and degranulation: Implications in severe asthma" @default.
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- W3035290143 doi "https://doi.org/10.1111/all.14450" @default.
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