Treatment of mast cells with carbon dioxide suppresses degranulation via a novel mechanism involving repression of increased intracellular calcium levels

Allergy. 2011 Mar;66(3):341-50. doi: 10.1111/j.1398-9995.2010.02482.x. Epub 2010 Sep 7.


Background: Intranasal noninhaled delivery of carbon dioxide (CO₂) is efficacious in the symptomatic treatment of seasonal allergic rhinitis. The goal of this study was to determine whether and how 100% CO₂ inhibits mast cell degranulation, thereby possibly contributing to the reduction of symptoms in seasonal allergic rhinitis.

Methods: Peritoneal mast cells isolated from rats and labelled with sulforhodamine-B (SFRM-B) were used to determine whether CO₂ treatment could block mast cell degranulation and histamine release in response to 48/80. In addition, the effect of CO₂ on intracellular calcium levels in unstimulated and stimulated mast cells was determined by fluorescent microscopy.

Results: Treatment with 48/80 caused >90% of mast cells containing SFRM-B to degranulate, resulting in a marked decrease in the fluorescent intensity within the mast cells, and simultaneously causing a significant increase in histamine release. Significantly, the stimulatory effect of 48/80 on fluorescent intensity and histamine levels was greatly inhibited (>95%) to near control levels by pretreatment with 100% CO₂. Treatment with 48/80 also caused a robust transient increase in intracellular calcium, whereas pretreatment with CO₂ repressed the increase in calcium (>70%) in response to 48/80.

Conclusions: Results from this study provide the first evidence of a unique regulatory mechanism by which CO₂ inhibits mast cell degranulation and histamine release by repressing stimulated increases in intracellular calcium. Thus, our data provide a plausible explanation for the reported therapeutic benefit of noninhaled intranasal delivery of 100% CO₂ to treat allergic rhinitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Carbon Dioxide / pharmacology*
  • Cell Degranulation / drug effects*
  • Cells, Cultured
  • Formaldehyde / pharmacology
  • Histamine Release / drug effects
  • Immunosuppressive Agents / pharmacology
  • Intracellular Space / drug effects*
  • Intracellular Space / metabolism
  • Male
  • Mast Cells / drug effects*
  • Mast Cells / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • p-Methoxy-N-methylphenethylamine / pharmacology


  • Immunosuppressive Agents
  • Carbon Dioxide
  • Formaldehyde
  • p-Methoxy-N-methylphenethylamine
  • Calcium