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

Immunity. 2015 Feb 17;42(2):279-293. doi: 10.1016/j.immuni.2015.01.015.

Abstract

Crosslinking of the immunoglobulin receptor FcεRI 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 FcεRI 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. FcεRI 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 FcεRI crosslinking. Thus, ATP released by FcεRI crosslinking stimulates basophils and mast cells for further activation causing allergic inflammation. E-NPP3 decreases ATP concentration and suppresses basophil and mast cell activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Asthma / immunology*
  • Basophils / cytology
  • Basophils / immunology*
  • Dermatitis, Contact / immunology
  • Diarrhea / immunology
  • Diarrhea / pathology
  • Immunoglobulin E / immunology
  • Mast Cells / cytology
  • Mast Cells / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Passive Cutaneous Anaphylaxis / immunology
  • Phosphoric Diester Hydrolases / genetics
  • Phosphoric Diester Hydrolases / immunology*
  • Pyrophosphatases / genetics
  • Pyrophosphatases / immunology*
  • RNA Interference
  • RNA, Small Interfering
  • Receptors, IgE / immunology*
  • Receptors, Purinergic P2X7 / genetics
  • Receptors, Purinergic P2X7 / immunology
  • Trinitrobenzenes / immunology

Substances

  • E-NPP3 protein, mouse
  • P2rx7 protein, mouse
  • RNA, Small Interfering
  • Receptors, IgE
  • Receptors, Purinergic P2X7
  • Trinitrobenzenes
  • Immunoglobulin E
  • Adenosine Triphosphate
  • Phosphoric Diester Hydrolases
  • Pyrophosphatases