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

Summary Background P2Y10, along with GPR34 and GPR174, is a G protein‐coupled receptor that is activated by an endogenous lipid mediator lysophosphatidylserine (LysoPS). Its expression pattern and its function are completely unknown. We have previously shown that P2Y10 is one of the highly up‐regulated genes at the late differentiation stage during in vitro eosinophilopoiesis. Objective We explored the expression and functions of P2Y10 in human cord blood (CB)‐derived and peripheral blood (PB) eosinophils. Methods Real‐time PCR, FACS, Western blot, ELISA, and chemotaxis assays were performed to determine the expression and function of P2Y10. Results As CB cells differentiated towards eosinophils, P2Y10 mRNA and protein were abundantly expressed. P2Y10 was the most highly expressed in the granulocytes from PB, to a lesser extent in monocytes, and least in lymphocytes. Further fractionation of granulocytes revealed that eosinophils express P2Y10 much more strongly than do neutrophils. PB eosinophils solely expressed P2Y10 among the three LysoPS receptors, while PB neutrophils expressed the three at comparable levels. LysoPS activated both CB and PB eosinophils to induce a robust ERK phosphorylation. Importantly, LysoPS was capable of triggering degranulation of ECP in PB eosinophils. This response was significantly reduced by pharmacological inhibitors of TNF‐alpha‐converting enzyme (TACE), epidermal growth factor receptor (EGFR), and ERK1/2, which were known to be required in P2Y10‐mediated signalling pathways. However, LysoPS had no effect on chemotaxis, differentiation, or eosinophil survival. Conclusions and Clinical Relevance LysoPS provokes eosinophil degranulation through P2Y10. Therefore, P2Y10 is a potential therapeutic target to control eosinophil‐associated diseases.