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


Background: Intranasal noninhaled delivery of carbon dioxide (CO 2) is efficacious in the symptomatic treatment of seasonal allergic rhinitis. The goal of this study was to determine whether and how 100% CO 2 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 CO 2 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.


JVIC-Center for Biomedical and Life Sciences

Document Type





48/80, allergic rhinitis, calcium, carbon dioxide, histamine, mast cells

Publication Date


Journal Title

Allergy: European Journal of Allergy and Clinical Immunology