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Publication : The ectoenzyme E-NPP3 negatively regulates ATP-dependent chronic allergic responses by basophils and mast cells.

First Author  Tsai SH Year  2015
Journal  Immunity Volume  42
Issue  2 Pages  279-293
PubMed ID  25692702 Mgi Jnum  J:223825
Mgi Id  MGI:5660449 Doi  10.1016/j.immuni.2015.01.015
Citation  Tsai SH, et al. (2015) The ectoenzyme E-NPP3 negatively regulates ATP-dependent chronic allergic responses by basophils and mast cells. Immunity 42(2):279-93
abstractText  Crosslinking of the immunoglobulin receptor FcepsilonRI activates basophils and mast cells to induce immediate and chronic allergic inflammation. However, it remains unclear how the chronic allergic inflammation is regulated. Here, we showed that ecto-nucleotide pyrophosphatase-phosphodiesterase 3 (E-NPP3), also known as CD203c, rapidly induced by FcepsilonRI crosslinking, negatively regulated chronic allergic inflammation. Basophil and mast cell numbers increased in Enpp3(-/-) mice with augmented serum ATP concentrations. Enpp3(-/-) mice were highly sensitive to chronic allergic pathologies, which was reduced by ATP blockade. FcepsilonRI crosslinking induced ATP secretion from basophils and mast cells, and ATP activated both cells. ATP clearance was impaired in Enpp3(-/-) cells. Enpp3(-/-)P2rx7(-/-) mice showed decreased responses to FcepsilonRI crosslinking. Thus, ATP released by FcepsilonRI crosslinking stimulates basophils and mast cells for further activation causing allergic inflammation. E-NPP3 decreases ATP concentration and suppresses basophil and mast cell activity.
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