title: Treatment of mast cells with carbon dioxide suppresses degranulation via a novel mechanism involving repression of increased intracellular calcium levels.
abstract: 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.
authors.affiliation: Center for Biomedical & Life Sciences, Missouri State University, Springfield, MO, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Strider
authors.forename: C G
authors.initials: CG
authors.lastname: Masterson
authors.forename: P L
authors.initials: PL
authors.lastname: Durham
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002245:Carbon Dioxide / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects*; D002478:Cells, Cultured; D005557:Formaldehyde / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D007166:Immunosuppressive Agents; D002245:Carbon Dioxide; D005557:Formaldehyde; D003189:p-Methoxy-N-methylphenethylamine; D002118:Calcium