Asthma: A comparison of animal models using stereological methods

D. M. Hyde, Lisa Miller, Edward S Schelegle, M. V. Fanucchi, L. S. Van Winkle, N. K. Tyler, Mark V Avdalovic, M. J. Evans, R. Kajekar, Alan R Buckpitt, Kent E Pinkerton, J. P. Joad, L. J. Gershwine, Reen Wu, Charles Plopper

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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 postnatal 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. Copyright

Original languageEnglish (US)
Pages (from-to)122-135
Number of pages14
JournalEuropean Respiratory Review
Volume15
Issue number101
DOIs
StatePublished - Dec 1 2006

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Keywords

  • Airway
  • Epithelial-mesenchymal trophic unit
  • Immune/inflammatory cells
  • Respiratory bronchiole

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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