P2X4イオンチャネル型受容体を介した肥満細胞機能およびアレルギー反応のプリン作動性調節

抄録

Mast cells are highly reactive and release a variety of mediators that cause allergic and inflammatory reactions. The most well-known mechanism of mast cell activation is antigen-induced aggregation of IgE-binding FcεRI complexes on the cell surface. The IgE-dependent mast cell activation is regulated by various humoral factors that lower the threshold for antigen-mediated activation, exacerbating allergic reactions. Recently, we found that extracellular ATP is an important factor in enhancing mast cell response to weak signals elicited by IgE-dependent as well as -independent mechanisms. Mast cells express many functional P2 receptors, but ATP-induced synergistic mast cell activation to antigens and G protein-coupled receptor agonists, such as PGE₂, adenosine and compound 48/80 were exclusively mediated by ionotropic P2X4 receptors. In addition, genetic and pharmacological inhibition of P2X4 receptor improved the IgE-dependent and -independent anaphylactic responses in vivo. Since ATP is a ubiquitous intercellular mediator that coexists with other chemical mediators, P2X4 receptor signal should play an important role in mast cell-dependent allergic reaction in vivo. In this symposium, we will introduce the unique effects of P2X4 receptor signals on various mast cell activation mechanisms found in our laboratory.