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Treatment of mast cells with carbon dioxide suppresses degranulation via a novel mechanism involving repression of increased intracellular calcium levels
Author(s) -
Strider J. W.,
Masterson C. G.,
Durham P. L.
Publication year - 2011
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2010.02482.x
Subject(s) - degranulation , histamine , calcium , mast cell , calcium in biology , intracellular , chemistry , pharmacology , immunology , endocrinology , medicine , biochemistry , receptor
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.