UDP/P2Y6 receptor signaling regulates IgE-dependent degranulation in human basophils
UDP/P2Y6 receptor signaling regulates IgE-dependent degranulation in human basophils
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DOI：
10.1016/j.alit.2017.02.014
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发表时间：
2017-10-01
影响因子：
6.8
通讯作者：
Takami, Hideki
中科院分区：
文献类型：
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作者：
Nakano, Manabu;Ito, Koichi;Takami, Hideki
背景：P2 Y嘌呤能受体（P2 YR）是一种G蛋白偶联受体，受细胞外核苷酸刺激。它们通过调节cAMP产生、蛋白激酶C激活、三磷酸肌醇产生和细胞内钙释放来介导细胞效应。该家族的P2 Y 6受体被UDP选择性地刺激，并被MRS 2578选择性地抑制。在本研究中，我们研究了UDP/P2 Y 6受体信号转导对IgE依赖的人嗜碱性粒细胞脱粒的影响。RTPCR检测P2 YR和ENTPDase基因的mRNA表达。使用钙探针检测嗜碱性粒细胞中通过UDP/P2 Y 6受体信号传导的细胞内Ca 2+内流。UDP/P2 Y 6受体信号传导对嗜碱性粒细胞中IgE依赖性脱粒的影响通过流式细胞术测量CD 63表达来证实。结果：纯化的嗜碱性粒细胞表达P2 Y 6 mRNA，UDP可使细胞内Ca ~（2+）增加，而MRS 2578可使细胞内Ca ~（2+）减少。UDP促进IgE依赖性脱颗粒。此外，MRS 2578抑制嗜碱性粒细胞中IgE依赖性脱粒。HPLC分析表明嗜碱性粒细胞自发分泌UTP。此外，嗜碱性粒细胞表达胞外核苷酸水解酶ENTPDase 2、ENTPDase 3和ENTPDase 8。结论：UDP/P2 Y 6受体信号通路参与了嗜碱性粒细胞IgE依赖性脱颗粒的调节，可能通过自分泌UTP刺激P2 Y 6受体。因此，该受体代表了在过敏性疾病期间调节嗜碱性粒细胞中IgE依赖性脱粒的潜在靶点。Copyright（C）2017，日本变态反应学会.制作和主办：Elsevier B. V.
Background: P2Y purinergic receptors (P2YR) are G protein-coupled receptors that are stimulated by extracellular nucleotides. They mediate cellular effects by regulating cAMP production, protein kinase C activation, inositol trisphosphate generation, and Ca2+ release from intracellular stores. The P2Y6 receptor of this family is selectively stimulated by UDP, and selectively inhibited by MRS2578. In the present study, we examined the effect of UDP/P2Y6 receptor signaling on IgE-dependent degranulation in human basophils.Methods: Basophils were purified from human peripheral blood. The mRNA expression of genes encoding P2YR and ecto-nucleoside triphosphate diphosphohydrolase (ENTPDase) was measured by RTPCR. Intracellular Ca2+ influx via UDP/P2Y6 receptor signaling in basophils was detected using a calcium probe. The effect of UDP/P2Y6 receptor signaling on IgE-dependent degranulation in basophils was confirmed by measuring CD63 expression by flow cytometry. Autocrine secretion of nucleotides was detected by HPLC analysis.Results: We showed that purified basophils express P2Y6 mRNA and that UDP increased intracellular Ca2+, which was reduced by MRS2578 treatment. UDP promoted IgE-dependent degranulation. Furthermore, MRS2578 inhibited IgE-dependent degranulation in basophils. HPLC analysis indicated that basophils spontaneously secrete UTP. In addition, basophils expressed the extracellular nucleotide hydrolases ENTPDase2, ENTPDase3, and ENTPDase8.Conclusions: This study showed that UDP/P2Y6 receptor signaling is involved in the regulation of IgE-dependent degranulation in basophils, which might stimulate the P2Y6 receptor via the autocrine secretion of UTP. Thus, this receptor represents a potential target to regulate IgE-dependent degranulation in basophils during allergic diseases. Copyright (C) 2017, Japanese Society of Allergology. Production and hosting by Elsevier B.V.