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Published ahead of print on July 11, 2003, doi:10.1164/rccm.200210-1188OC

Am. J. Respir. Crit. Care Med., Volume 168, Number 8, October 2003, 959-967

A more recent version of this article appeared on October 15, 2003
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Submitted on November 19, 2002
Accepted on July 2, 2003

Mouse model of airway remodeling - strain differences -

Kazuhiko Shinagawa1* and Masami Kojima1

1 Pharmacology Laboratory, Kissei Pharmaceutical Company, Ltd., Hotaka, Nagano, Japan

* To whom correspondence should be addressed. E-mail: kazuhiko_shinagawa{at}pharm.kissei.co.jp.

We found that continuous eosinophilic inflammation following repeated antigen-instillation into the nose was observed only in A/J mice, not in three other strains. Histological 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 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 airway hyperresponsiveness was observed in the former strain. In C57BL/6 and C3H/HeJ mice, eosinophilic inflammation, airway-wall thickening, and airway hyperresponsiveness 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 following OVA/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 histological changes in the lungs may be obtainable using this model.
Key words: Asthma, eosinophil, airway hyperresponsiveness, A/J mouse




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