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Published ahead of print on July 11, 2003, doi:10.1164/rccm.200210-1188OC
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American Journal of Respiratory and Critical Care Medicine Vol 168. pp. 959-967, (2003)
© 2003 American Thoracic Society

Mouse Model of Airway Remodeling

Strain Differences

Kazuhiko Shinagawa and Masami Kojima

Pharmacology Lab, Kissei Pharmaceutical Co. Ltd., Nagano, Japan

Correspondence and requests for reprints should be addressed to Kazuhiko Shinagawa, Pharmacology Lab, Kissei Pharmaceutical Co. Ltd., 4365-1, Kashiwabara, Hotaka, Minamiazumi, Nagano 399-8304, Japan. E-mail: kazuhiko_shinagawa{at}pharm.kissei.co.jp

We found that continuous eosinophilic inflammation after repeated antigen instillation into the nose was observed only in A/J mice, not in three other strains. Histologic analysis of tissues from A/J mice revealed features typical of airway remodeling, i.e., airway wall thickening and increased collagen depositions were observed after 12 weeks' antigen exposure. Persistent airway hyperresponsiveness (AHR) was observed in chronically antigen-exposed A/J mice. Eosinophilic inflammation, collagen deposition, and airway wall thickening were all less marked in BALB/c mice than in A/J mice, and no AHR was observed in the former strain. In C57BL/6 and C3H/HeJ mice, eosinophilic inflammation, airway wall thickening, and AHR were not observed at all, although slightly increased collagen deposition was observed. Thus, we found that these changes were strain-dependent. On the other hand, in A/J mice inhalational antigen challenge after ovalbumin/alum immunization led only to a transient increase in eosinophils and to less airway wall thickening, indicating the importance of the protocol used. Use of A/J mice and giving antigen by instillation via the nose is to be recommended for studies of the mechanisms underlying asthma. In particular, useful qualitative and quantitative information relating to the structural and histologic changes in the lungs may be obtainable using this model.

Key Words: asthma • eosinophil • airway hyperresponsiveness • A/J mouse




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