UDP/P2Y6 receptor signaling regulates IgE-dependent degranulation in human basophils

Allergol Int. 2017 Oct;66(4):574-580. doi: 10.1016/j.alit.2017.02.014. Epub 2017 Mar 17.


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 RT-PCR. 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.

Keywords: Basophil; IgE-dependent degranulation; MRS2578; P2Y6; UDP.

MeSH terms

  • Adult
  • Basophils / drug effects
  • Basophils / immunology*
  • Basophils / metabolism*
  • Calcium / metabolism
  • Cell Degranulation / drug effects
  • Cell Degranulation / immunology*
  • Cell Survival / drug effects
  • Cell Survival / immunology
  • Gene Expression
  • Healthy Volunteers
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology*
  • Isothiocyanates / pharmacology
  • Pyrophosphatases / genetics
  • Pyrophosphatases / metabolism
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2 / metabolism*
  • Signal Transduction*
  • Thiourea / analogs & derivatives
  • Thiourea / pharmacology
  • Uridine Diphosphate / metabolism*
  • Uridine Triphosphate / metabolism
  • Young Adult


  • Isothiocyanates
  • N,N''-1,4-butanediylbis(N'-(3-isothiocyanatophenyl))thiourea
  • Receptors, Purinergic P2
  • purinoceptor P2Y6
  • Immunoglobulin E
  • Uridine Diphosphate
  • Pyrophosphatases
  • nucleoside-triphosphate diphosphohydrolase 3
  • Thiourea
  • Calcium
  • Uridine Triphosphate