TY - JOUR
T1 - An improved murine model of asthma
T2 - Selective airway inflammation, epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen
AU - Temelkovski, Jason
AU - Hogan, Simon P.
AU - Shepherd, Darren P.
AU - Foster, Paul S.
AU - Kumar, Rakesh K.
PY - 1998
Y1 - 1998
N2 - Background - Existing murine models of asthma lack many of the inflammatory and epithelial changes that are typical of the human disease. Moreover, these models are frequently complicated by allergic alveolitis. Methods - High IgE responder BALB/c mice were systemically sensitised to ovalbumin and chronically challenged with low particle mass concentrations of aerosolised ovalbumin. Titres of antiovalbumin IgE in serum were measured at two weekly intervals by enzyme immunoassay, accumulation of inflammatory cells and histopathological abnormalities of the epithelium were quantified morphometrically in the trachea and the lungs, and airway reactivity was assessed by measuring bronchoconstriction following intravenous administration of methacholine. Results - Mice sensitised by two intraperitoneal injections of ovalbumin developed high titres of IgE antibodies to ovalbumin. Following exposure to low concentrations of aerosolised antigen for up to eight weeks these animals developed a progressive inflammatory response in the airways, characterised by the presence of intraepithelial eosinophils and by infiltration of the lamina propria with lymphoid/mononuclear cells, without associated alveolitis. Goblet cell hyperplasia/metaplasia was induced in the intrapulmonary airways, while epithelial thickening and subepithelial fibrosis were evident following chronic exposure. In parallel, the mice developed increased sensitivity to induction of bronchospasm, as well as increased maximal reactivity. Non- immunised mice exposed to aerosolised ovalbumin had low or absent antiovalbumin IgE and did not exhibit inflammatory or epithelial changes, but developed airway hyperreactivity. Conclusions - This experimental model replicates many of the features of human asthma and should facilitate studies of pathogenetic mechanisms and of potential therapeutic agents.
AB - Background - Existing murine models of asthma lack many of the inflammatory and epithelial changes that are typical of the human disease. Moreover, these models are frequently complicated by allergic alveolitis. Methods - High IgE responder BALB/c mice were systemically sensitised to ovalbumin and chronically challenged with low particle mass concentrations of aerosolised ovalbumin. Titres of antiovalbumin IgE in serum were measured at two weekly intervals by enzyme immunoassay, accumulation of inflammatory cells and histopathological abnormalities of the epithelium were quantified morphometrically in the trachea and the lungs, and airway reactivity was assessed by measuring bronchoconstriction following intravenous administration of methacholine. Results - Mice sensitised by two intraperitoneal injections of ovalbumin developed high titres of IgE antibodies to ovalbumin. Following exposure to low concentrations of aerosolised antigen for up to eight weeks these animals developed a progressive inflammatory response in the airways, characterised by the presence of intraepithelial eosinophils and by infiltration of the lamina propria with lymphoid/mononuclear cells, without associated alveolitis. Goblet cell hyperplasia/metaplasia was induced in the intrapulmonary airways, while epithelial thickening and subepithelial fibrosis were evident following chronic exposure. In parallel, the mice developed increased sensitivity to induction of bronchospasm, as well as increased maximal reactivity. Non- immunised mice exposed to aerosolised ovalbumin had low or absent antiovalbumin IgE and did not exhibit inflammatory or epithelial changes, but developed airway hyperreactivity. Conclusions - This experimental model replicates many of the features of human asthma and should facilitate studies of pathogenetic mechanisms and of potential therapeutic agents.
KW - Asthma
KW - Epithelial abnormalities
KW - Mucosal inflammation
KW - Murine model
UR - http://www.scopus.com/inward/record.url?scp=0031781163&partnerID=8YFLogxK
U2 - 10.1136/thx.53.10.849
DO - 10.1136/thx.53.10.849
M3 - Article
SN - 0040-6376
VL - 53
SP - 849
EP - 856
JO - Thorax
JF - Thorax
IS - 10
ER -