Enhancement of goblet cell hyperplasia and airway hyperresponsiveness by salbutamol in a rat model of atopic asthma.
BACKGROUND
Goblet cell hyperplasia (GCH) is a prominent feature in animal models of atopic asthma produced by immunisation and following multiple challenges with antigens. The aim of this study was to examine the effect of a beta(2) agonist on the development of GCH induced by the immune response.


METHODS
Brown Norway rats were immunised and challenged with an aerosol of ovalbumin for four weeks. Salbutamol (0.5 mg/kg/day) or vehicle was continuously delivered for the four weeks using a subcutaneously implanted osmotic minipump. The density of goblet cells, other morphological changes, and airway responsiveness to methacholine were evaluated 24 hours after the final challenge.


RESULTS
Treatment with salbutamol induced a more than twofold increase in the mean (SE) number of goblet cells (53.7 (7.3) vs 114.5 (11.8) cells/10(3) epithelial cells, p<0.01) while it did not significantly influence airway wall thickening and eosinophilic infiltration. Airway responsiveness to methacholine expressed as the logarithmic value of the concentration of methacholine required to generate a 50% increase in airway pressure (logPC(150)Mch) was also enhanced by the beta(2) agonist (-0.56 (0. 21) vs -0.95 (0.05), p<0.05). Additional experiments revealed that the same dose of the beta(2) agonist alone did not cause GCH in non-immunised rats and that the enhancement of GCH by salbutamol was completely abolished by simultaneous treatment with methylprednisolone (0.5 mg/kg/day).


CONCLUSIONS
These data suggest that salbutamol enhances goblet cell hyperplasia and airway hyperresponsiveness in this rat model of atopic asthma.
Kamachi
A
A
First Department of Medicine, School of Medicine, Hokkaido University, Sapporo, Japan. caw35770@pop.21.odn.ne.jp
Munakata
M
M
Nasuhara
Y
Y
Nishimura
M
M
Ohtsuka
Y
Y
Amishima
M
M
Takahashi
T
T
Homma
Y
Y
Kawakami
Y
Y
D000318:Adrenergic beta-Agonists / Q000009:adverse effects*; D000420:Albuterol / Q000009:adverse effects*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001249:Asthma / Q000276:immunology / Q000473:pathology*; D016085:Bronchoconstrictor Agents; D004804:Eosinophils / Q000276:immunology; D020397:Goblet Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D006965:Hyperplasia / Q000139:chemically induced / Q000276:immunology; D008297:Male; D016210:Methacholine Chloride; D008775:Methylprednisolone / Q000627:therapeutic use; D023421:Models, Animal; D051381:Rats; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D000420:Albuterol; D008775:Methylprednisolone