title: Involvement of mast cells in adenosine-mediated bronchoconstriction and inflammation in an allergic mouse model.
abstract: In allergen-induced asthma, activation of lung mast cells leads to bronchial constriction, increased mucus secretion, and an increase in the localization of inflammatory cells to the airways. The purpose of this study was to explore the role of mast cells in adenosine-mediated airway reactivity and inflammation using the mast cell degranulating agent, compound 48/80 (C48/80). Mice were sensitized and challenged with ragweed (or 0.9% saline) followed by C48/80 administration twice a day in increasing doses for 5 days. Dose-responsiveness to the nonspecific adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) was established, and lung lavage was performed 24 h later for cell differential analysis to evaluate inflammation. At a dose of 375 microg/ml (aerosolized NECA), C48/80 pretreatment resulted in a significant attenuation in airway reactivity when compared with sensitized control mice (330.07 versus 581.57%, respectively). Lung lavage from the C48/80 treated mice showed a decrease in eosinophils (17.7 versus 60.9%, respectively) and an increase in macrophages when compared with the sensitized control group (76.4 versus 30.8%, respectively). These results support the conclusion that mast cell degranulation plays an important role in adenosine receptor-mediated airway hyperresponsiveness and inflammation.
authors.affiliation: Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Oldenburg
authors.forename: S Jamal
authors.initials: SJ
authors.lastname: Mustafa
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D031164:Ambrosia / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D002452:Cell Count; D015550:Cell Degranulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000503:physiopathology*; D007958:Leukocyte Count; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D018721:Muscarinic Agonists; D016210:Methacholine Chloride; D019830:Adenosine-5'-(N-ethylcarboxamide); D003189:p-Methoxy-N-methylphenethylamine; D000241:Adenosine