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Asthma: a comparison of animal models using stereological methods

D. M. Hyde^*,#, L. A. Miller^*,#, E. S. Schelegle^*,#, M. V. Fanucchi^*,#, L. S. Van Winkle^*,#, N. K. Tyler^*,#, M. V. Avdalovic^*,¶, M. J. Evans^*,#, R. Kajekar^*,#, A. R. Buckpitt^*,, K. E. Pinkerton^*,#,, J. P. Joad, L. J. Gershwin, R. Wu^*,#,¶ and C. G. Plopper^*,#

^* California National Primate Research Center, ^# Depts of Anatomy, Physiology and Cell Biology, Molecular Biosciences and Pathology, Microbiology and Immunology, School of Veterinary Medicine, ^¶ Depts of Medicine and Paediatrics, School of Medicine, University of California, Davis, CA, USA.

CORRESPONDENCE: D. M. Hyde, California National Primate Research Center, One Shields Avenue, University of California, Davis, CA 95616, USA. Fax: 1 5307546228. E-mail: dmhyde{at}primate.ucdavis.edu

Asthma is a worldwide health problem that affects 300 million people, as estimated by the World Health Organization. A key question in light of this statistic is: "what is the most appropriate laboratory animal model for human asthma?"

The present authors used stereological methods to assess airways in adults and during post-natal development, and their response to inhaled allergens to compare rodents and nonhuman primates to responses in humans.

An epithelial–mesenchymal trophic unit was defined in which all of the compartments interact with each other. Asthma manifests itself by altering not only the epithelial compartment but also other compartments (e.g. interstitial, vascular, immunological and nervous). All of these compartments show significant alteration in an airway generation-specific manner in rhesus monkeys but are limited to the proximal airways in mice. The rhesus monkey model shares many of the key features of human allergic asthma including the following: 1) allergen-specific immunoglobulin (Ig)E and skin-test positivity; 2) eosinophils and IgE+ cells in airways; 3) a T-helper type 2 cytokine profile in airways; 4) mucus cell hyperplasia; 5) subepithelial fibrosis; 6) basement membrane thickening; and 7) persistent baseline hyperreactivity to histamine or methacholine.

In conclusion, the unique responses to inhaled allergens shown in rhesus monkeys make it the most appropriate animal model of human asthma.

KEYWORDS: Airway, epithelial–mesenchymal trophic unit, immune/inflammatory cells, respiratory bronchiole