Premium
Lysophosphatidylserine induces eosinophil extracellular trap formation and degranulation: Implications in severe asthma
Author(s) -
Kim Hye Jeong,
Sim Myeong Seong,
Lee Dong Hyun,
Kim Chun,
Choi Youngwoo,
Park HaeSim,
Chung Il Yup
Publication year - 2020
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.14450
Subject(s) - degranulation , immunology , eosinophil , extracellular , neutrophil extracellular traps , eosinophil cationic protein , cytolysis , chemokine , inflammation , chemistry , microbiology and biotechnology , receptor , biology , asthma , in vitro , biochemistry , cytotoxicity
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.