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 language | English (US) |
|---|---|
| Pages (from-to) | 122-135 |
| Number of pages | 14 |
| Journal | European Respiratory Review |
| Volume | 15 |
| Issue number | 101 |
| DOIs | |
| State | Published - 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
Cite this
Asthma : A comparison of animal models using stereological methods. / Hyde, D. M.; Miller, Lisa; Schelegle, Edward S; Fanucchi, M. V.; Van Winkle, L. S.; Tyler, N. K.; Avdalovic, Mark V; Evans, M. J.; Kajekar, R.; Buckpitt, Alan R; Pinkerton, Kent E; Joad, J. P.; Gershwine, L. J.; Wu, Reen; Plopper, Charles.
In: European Respiratory Review, Vol. 15, No. 101, 01.12.2006, p. 122-135.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Asthma
T2 - A comparison of animal models using stereological methods
AU - Hyde, D. M.
AU - Miller, Lisa
AU - Schelegle, Edward S
AU - Fanucchi, M. V.
AU - Van Winkle, L. S.
AU - Tyler, N. K.
AU - Avdalovic, Mark V
AU - Evans, M. J.
AU - Kajekar, R.
AU - Buckpitt, Alan R
AU - Pinkerton, Kent E
AU - Joad, J. P.
AU - Gershwine, L. J.
AU - Wu, Reen
AU - Plopper, Charles
PY - 2006/12/1
Y1 - 2006/12/1
N2 - 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
AB - 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
KW - Airway
KW - Epithelial-mesenchymal trophic unit
KW - Immune/inflammatory cells
KW - Respiratory bronchiole
UR - http://www.scopus.com/inward/record.url?scp=34447123262&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34447123262&partnerID=8YFLogxK
U2 - 10.1183/09059180.00010103
DO - 10.1183/09059180.00010103
M3 - Article
AN - SCOPUS:34447123262
VL - 15
SP - 122
EP - 135
JO - European Respiratory Review
JF - European Respiratory Review
SN - 0905-9180
IS - 101
ER -