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: Yosuke Kurashima, Takeaki Amiya, Tomonori Nochi, Kumiko Fujisawa, Takeshi Haraguchi, Hideo Iba, Hiroko Tsutsui, Shintaro Sato, Sachiko Nakajima, Hideki Iijima, Masato Kubo, Jun Kunisawa, Hiroshi Kiyono
• Journal: Nature communications (Nat Commun) Vol. 3 Pg. 1034 ( 2012) ISSN: 2041-1723 [Electronic] England
• PMID: 22948816 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Receptors, Purinergic P2X7
• Adenosine Triphosphate

Topics

• Adenosine Triphosphate (immunology)
• Animals
• Cells, Cultured
• Crohn Disease (genetics, immunology)
• Cytokines (genetics, immunology)
• Female
• Humans
• Intestines (immunology)
• Mast Cells (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptors, Purinergic P2X7 (genetics, immunology)