Lysophosphatidylserine receptor P2Y10: A G protein‐coupled receptor that mediates eosinophil degranulation

Hwang, Soo Min; Kim, H. J.; Kim, S. M.; Jung, YunJae; Park, S. W.; Chung, Il Yup

doi:10.1111/cea.13162

Cited by 28 publications

(25 citation statements)

References 46 publications

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“…EoL-1 cells were maintained at 1 × 10 6 /mL in Roswell Park Memorial Institute (RPMI) 1640 medium (Sigma-Aldrich, St. Louis, MO, United States) supplemented with 10% fetal bovine serum in 5% CO 2 at 37 • C and differentiated by adding 0.5 µM butyrate (Sigma-Aldrich, St. Louis, MO, United States) for 2 days. To examine the effects of TLR ligands on the differentiated EoL-1 cells, butyratetreated EoL-1 cells were stimulated with poly(I:C) (10 µM, InvivoGen, San Diego, CA, United States), LPS (1 ng/mL, Sigma-Aldrich, St. Louis, MO, United States), palmitic acid (250 mM, Sigma-Aldrich, St. Louis, MO, United States), or R848 (1 µg/mL, InvivoGen, San Diego, CA, United States) for 24 h. Human eosinophils were differentiated from CB CD34 + cells for 24 days as previously described in detail (Hwang et al, 2016(Hwang et al, , 2018.…”

Section: Cell Culturementioning

confidence: 99%

“…We next checked expression levels of TLRs in EoL-1 cells and observed that transcripts of TLR3, TLR4, TLR7, TLR8, and TLR9 were significantly increased in dEoL-1 cells ( Figure 1A). Eosinophils arise from CD34 + hematopoietic stem cells (Rothenberg and Hogan, 2006), and we previously demonstrated that culturing CB CD34 + cells for 24 days with eosinophil lineage committed cytokines produces mature eosinophils (Hwang et al, 2016(Hwang et al, , 2018; Supplementary Figure S2). As shown in Figure 1B, we found apparent mRNA expression for TLR2, TLR4, TLR6, TLR8, and TLR9 in CB-derived eosinophils (FPKM > 1), and expression of TLR4 transcript was the highest compared to other TLRs (FPKM = 27.97 ± 1.67).…”

Section: Tlr Expression Is Induced In Differentiated Eol-1 Cells and mentioning

confidence: 99%

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Eosinophil Activation by Toll-Like Receptor 4 Ligands Regulates Macrophage Polarization

Yoon

Jang

et al. 2019

Front. Cell Dev. Biol.

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Eosinophils are terminally differentiated granulocytes that have long been considered as destructive cells associated with Th2 type immune responses such as allergic inflammation and helminth infections. Recently, eosinophils have been actively studied as multifunctional leukocytes regulating an array of physiological responses through interaction with other immune cells. In this study, we examined the expression and function of Toll-like receptors (TLRs) in eosinophilic EoL-1 cells and demonstrated the expression of a number of immune mediators in activated EoL-1 cells and their interaction with the macrophage cell line THP-1 upon TLR4 ligand stimulation. EoL-1 cells differentiated with butyrate increased expression of TLR3, TLR4, and TLR7 at mRNA and protein level with flow cytometry analysis. Mature eosinophils derived from human cord blood CD34 + cells were subjected to RNA-sequencing, and showed the expression of a panel of TLR transcripts and TLR4 was the most highly expressed TLR. Among the cognate ligands of TLR3, TLR4, and TLR7, lipopolysaccharide (LPS) or palmitic acid significantly increased mRNA expression of immune mediators in differentiated EoL-1 cells. Notably, Western blot analysis of palmitic acid-treated differentiated EoL-1 cells showed significantly up-regulated expression of Th2 type cytokines and transcription factors driving eosinophil differentiation. To evaluate functional significance of TLR4 ligand-stimulated eosinophils, we added conditioned media (CM) from EoL-1 cells to differentiated THP-1 cells and assessed the expression of M1 macrophage or M2 macrophage-related markers. M1 and M2 macrophage markers were significantly upregulated by CM from LPS and palmitic acid stimulated EoL-1 cells, respectively. In addition, the adipose tissue of obese mice, where eosinophils are decreased due to obesity-induced inflammation, showed significantly decreased frequency of M2 macrophages, despite an increase in the total macrophage numbers. Based on these collective data, we proposed that eosinophils regulate both inflammatory and anti-inflammatory polarization of macrophages through functional changes induced by different TLR4 ligands.

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Section: Cell Culturementioning

confidence: 99%

Section: Tlr Expression Is Induced In Differentiated Eol-1 Cells and mentioning

confidence: 99%

Eosinophil Activation by Toll-Like Receptor 4 Ligands Regulates Macrophage Polarization

Yoon

Jang

et al. 2019

Front. Cell Dev. Biol.

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“…5 Our previous study demonstrated that when PB eosinophils were exposed to LysoPS at 10 μmol/L or less for four days, survival/apoptosis of LysoPS-treated eosinophils was not significantly different from those of untreated eosinophils. 28 However, further experiments showed that detectable amounts of LDH were released upon exposure to 10 μmol/L LysoPS for Figure 1Ai). The DNA filaments in EETs from LysoPS-stimulated eosinophils were preferentially projected toward neighboring cells, suggesting that cohesion of eosinophil DNA traps is contact-dependent.…”

Section: Lysops Induces Eosinophil Extracellular Trap Formationmentioning

confidence: 92%

“…Although LysoPS does not induce chemotaxis or affect cell survival/ apoptosis, eosinophils from patients with blood eosinophilia release detectable amounts of eosinophil cationic protein (ECP) in response to 10 μmol/L LysoPS. 28 Two other lysophospholipids affect eosinophil functions in addition to LysoPS. Lysophosphatidic acid induces eosinophil chemotaxis and upregulates adhesion molecules in a range of ~10 -5 -10 -3 M in a pertussis toxin (PTX)-dependent manner, 29 while lysoplatelet-activating factor (LysoPAF) triggers eosinophil degranulation at ~10 -6 M independently of PTX and is more potent than PAF.…”

Section: G R a P H I C A L Abstractmentioning

confidence: 99%

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Lysophosphatidylserine induces eosinophil extracellular trap formation and degranulation: Implications in severe asthma

Kim

Sim

Lee

et al. 2020

Allergy

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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 plateletactivating 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.

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The Lysophosphatidylserines—An Emerging Class of Signalling Lysophospholipids

et al. 2020

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Lysophosphatidylserine receptor P2Y10: A G protein‐coupled receptor that mediates eosinophil degranulation

Abstract: LysoPS provokes eosinophil degranulation through P2Y10. Therefore, P2Y10 is a potential therapeutic target to control eosinophil-associated diseases.

Cited by 28 publications

References 46 publications

Eosinophil Activation by Toll-Like Receptor 4 Ligands Regulates Macrophage Polarization

Eosinophil Activation by Toll-Like Receptor 4 Ligands Regulates Macrophage Polarization

Lysophosphatidylserine induces eosinophil extracellular trap formation and degranulation: Implications in severe asthma

The Lysophosphatidylserines—An Emerging Class of Signalling Lysophospholipids

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