Induction, Duration, and Resolution of Airway Goblet Cell Hyperplasia in a Murine Model of Atopic Asthma: Effect of Concurrent Infection with Respiratory Syncytial Virus and Response to Dexamethasone

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Abstract
We recently described a murine model of atopic asthma in which a marked, extensive hyperplasia of air- way goblet cells is induced by repeated challenge of ovalbumin (OA)-sensitized mice with intratracheally administered allergen ( Am. J. Respir. Cell Mol. Biol. 1996;14:425-438). We report here the time course of the duration of this feature and of its spontaneous resolution in the absence of further allergen exposure. Induction of severe neutrophilic inflammation in the airways by repeated intratracheal administration of li- popolysaccharide failed to induce goblet cell hyperplasia (GCH) to as great a degree as that induced by al- lergen, suggesting that nonallergic inflammation is a relatively poor inducer of this phenotype change in mice. When a "subclinical" infection of the lungs with the human A2 strain of respiratory syncytial virus was superimposed on the model of atopic asthma, recruitment of monocytes and lymphocytes to the air- ways was enhanced and a discharge of goblet cell mucin contents was observed. This may partly explain the respiratory difficulty that typifies virally induced exacerbations of asthma in humans. Daily systemic treatment of sensitized mice with dexamethasone during the period of allergen challenge produced a dose- related suppression of developing GCH, while similar treatment during the period following the establish- ment of extensive hyperplasia induced an accelerated resolution toward a normal epithelial phenotype. These results confirm and extend the relevance of this model as a representation of the human disease. Blyth, D. I., M. S. Pedrick, T. J. Savage, H. Bright, J. E. Beesley, and S. Sanjar. 1998. Induction, du- ration, and resolution of airway goblet cell hyperplasia in a murine model of atopic asthma: effect of concurrent infection with respiratory syncytial virus and response to dexamethasone. Am. J. Respir. Cell Mol. Biol. 19:38-54. A marked increase in the numbers of goblet cells in airway epithelium occurs in asthma and chronic bronchitis (1, 2). The resulting overproduction of mucin contributes to air- way obstruction (3) and makes it difficult for patients to clear their chests. We have used a murine model of atopic asthma to investigate various aspects of goblet cell hyper- plasia (GCH), with the aim of eventually defining its role in the disease and its response to therapy. In previously published work we showed that a marked and extensive GCH develops in the airways of ovalbumin (OA)-sensitized mice following repeated intratracheal challenge with the allergen (4). This dose-related increase