title: Extracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors.
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 Kit(W-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.
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 108-8639, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kurashima
authors.forename: Takeaki
authors.initials: T
authors.lastname: Amiya
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nochi
authors.forename: Kumiko
authors.initials: K
authors.lastname: Fujisawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Haraguchi
authors.forename: Hideo
authors.initials: H
authors.lastname: Iba
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sato
authors.forename: Sachiko
authors.initials: S
authors.lastname: Nakajima
authors.forename: Hideki
authors.initials: H
authors.lastname: Iijima
authors.forename: Masato
authors.initials: M
authors.lastname: Kubo
authors.forename: Jun
authors.initials: J
authors.lastname: Kunisawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000255:Adenosine Triphosphate / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007422:Intestines / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate