title: Differential effects of allergen challenge on large and small airway reactivity in mice.
abstract: The relative contributions of large and small airways to hyperresponsiveness in asthma have yet to be fully assessed. This study used a mouse model of chronic allergic airways disease to induce inflammation and remodelling and determine whether in vivo hyperresponsiveness to methacholine is consistent with in vitro reactivity of trachea and small airways. Balb/C mice were sensitised (days 0, 14) and challenged (3 times/week, 6 weeks) with ovalbumin. Airway reactivity was compared with saline-challenged controls in vivo assessing whole lung resistance, and in vitro measuring the force of tracheal contraction and the magnitude/rate of small airway narrowing within lung slices. Increased airway inflammation, epithelial remodelling and fibrosis were evident following allergen challenge. In vivo hyperresponsiveness to methacholine was maintained in isolated trachea. In contrast, methacholine induced slower narrowing, with reduced potency in small airways compared to controls. In vitro incubation with IL-1/TNFα did not alter reactivity. The hyporesponsiveness to methacholine in small airways within lung slices following chronic ovalbumin challenge was unexpected, given hyperresponsiveness to the same agonist both in vivo and in vitro in tracheal preparations. This finding may reflect the altered interactions of small airways with surrounding parenchymal tissue after allergen challenge to oppose airway narrowing and closure.
authors.affiliation: Lung Health Research Centre, Department of Pharmacology & Therapeutics, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Chantal
authors.initials: C
authors.lastname: Donovan
authors.forename: Simon G
authors.initials: SG
authors.lastname: Royce
authors.forename: James
authors.initials: J
authors.lastname: Esposito
authors.forename: Jenny
authors.initials: J
authors.lastname: Tran
authors.forename: Zaridatul Aini
authors.initials: ZA
authors.lastname: Ibrahim
authors.forename: Mimi L K
authors.initials: ML
authors.lastname: Tang
authors.forename: Simon
authors.initials: S
authors.lastname: Bailey
authors.forename: Jane E
authors.initials: JE
authors.lastname: Bourke
mesh_terms: D056151:Airway Remodeling; D000485:Allergens / Q000276:immunology*; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001985:Bronchial Provocation Tests; D002118:Calcium / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016210:Methacholine Chloride / Q000008:administration & dosage; D051379:Mice; D010047:Ovalbumin / Q000276:immunology
chemical_list: D000485:Allergens; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D010047:Ovalbumin; D015232:Dinoprostone; D002118:Calcium
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