Extracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors

Yosuke Kurashima, Takeaki Amiya, Tomonori Nochi, Kumiko Fujisawa, Takeshi Haraguchi, Hideo Iba, Hiroko Tsutsui, Shintaro Sato, Sachiko Nakajima, Hideki Iijima, Masato Kubo, Jun Kunisawa () and Hiroshi Kiyono ()
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Yosuke Kurashima: The Institute of Medical Science, The University of Tokyo
Takeaki Amiya: The Institute of Medical Science, The University of Tokyo
Tomonori Nochi: The Institute of Medical Science, The University of Tokyo
Kumiko Fujisawa: The Institute of Medical Science, The University of Tokyo
Takeshi Haraguchi: The Institute of Medical Science, The University of Tokyo
Hideo Iba: The Institute of Medical Science, The University of Tokyo
Hiroko Tsutsui: Hyogo College of Medicine
Shintaro Sato: The Institute of Medical Science, The University of Tokyo
Sachiko Nakajima: Osaka University Graduate School of Medicine
Hideki Iijima: Osaka University Graduate School of Medicine
Masato Kubo: Research Center for Allergy and Immunology, RIKEN, Yokohama Institute, Tsurumi, Yokohama
Jun Kunisawa: The Institute of Medical Science, The University of Tokyo
Hiroshi Kiyono: The Institute of Medical Science, The University of Tokyo

Nature Communications, 2012, vol. 3, issue 1, 1-12

Abstract: Abstract Mast cells are known effector cells in allergic and inflammatory diseases, but their precise roles in intestinal inflammation remain unknown. Here we show that activation of mast cells in intestinal inflammation is mediated by ATP-reactive P2X7 purinoceptors. We find an increase in the numbers of mast cells expressing P2X7 purinoceptors in the colons of mice with colitis and of patients with Crohn's disease. Treatment of mice with a P2X7 purinoceptor-specific antibody inhibits mast cell activation and subsequent intestinal inflammation. Similarly, intestinal inflammation is ameliorated in mast cell-deficient KitW-sh/W-sh mice, and reconstitution with wild-type, but not P2x7−/− mast cells results in susceptibility to inflammation. ATP-P2X7 purinoceptor-mediated activation of mast cells not only induces inflammatory cytokines, but also chemokines and leukotrienes, to recruit neutrophils and subsequently exacerbate intestinal inflammation. These findings reveal the role of P2X7 purinoceptor-mediated mast cell activation in both the initiation and exacerbation of intestinal inflammation.

Date: 2012
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DOI: 10.1038/ncomms2023

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