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

To cite this article: Strider JW, Masterson CG, Durham PL. Treatment of mast cells with carbon dioxide suppresses degranulation via a novel mechanism involving repression of increased intracellular calcium levels. Allergy 2011; 66 : 341–350. Abstract 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 CO 2 treatment could block mast cell degranulation and histamine release in response to 48/80. In addition, the effect of CO 2 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% CO 2. 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 CO 2 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% CO 2 to treat allergic rhinitis.