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.
We recently described a murine model of atopic asthma in which a marked, extensive hyperplasia of airway 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 lipopolysaccharide failed to induce goblet cell hyperplasia (GCH) to as great a degree as that induced by allergen, 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 airways 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 establishment 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
DI
Respiratory Diseases, Molecular Pathology and Systems Biology Units, Glaxo Wellcome Research and Development, Stevenage, Hertfordshire, United Kingdom.
Pedrick
M S
MS
Savage
T J
TJ
Bright
H
H
Beesley
J E
JE
Sanjar
S
S
D000485:Allergens; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001249:Asthma / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003907:Dexamethasone / Q000627:therapeutic use*; D004804:Eosinophils; D004847:Epithelial Cells / Q000473:pathology; D006965:Hyperplasia; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000473:pathology*; D008214:Lymphocytes; D008264:Macrophages; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils; D010047:Ovalbumin / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000150:complications*; D012141:Respiratory Tract Infections / Q000150:complications*
D000485:Allergens; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D003907:Dexamethasone; D010047:Ovalbumin