LUNG INFLAMMATION AND EPITHELIAL CHANGES IN A MURINE MODEL OF ATOPIC ASTHMA

A murine model of allergen-induced airway inflammation and epithelial phenotypic change, and the time-courses of these events, are described . Mice were sensitized to ovalbumin using an adjuvant-free protocol, a nd challenged by multiple intratracheal instillations of ovalbumin by a non-surgical technique. Many of the characteristic features of human atopic asthma were seen in the mice. A marked eosinophilic infiltrati on of lung tissue and airways followed allergen challenge, and its sev erity increased with each challenge, as did the number of eosinophils in the blood. Lymphocytes, neutrophils, and monocytes also invaded the lungs. Airway macrophages showed signs of activation, their appearanc e resembling those recovered from antigen-challenged human asthmatic a irways. The airway epithelium was thickened and displayed a marked gob let cell hyperplasia in terminal bronchioles and larger airways. After repeated challenges, the reticular layer beneath the basement membran e of the airway epithelium showed fibrosis, reproducing a commonly obs erved histologic feature of human asthma. Goblet cell hyperplasia bega n to appear before eosinophils or lymphocytes had migrated across the airway epithelium, and persisted for at least 11 days after the third intratracheal challenge with ovalbumin, despite the number of inflamma tory cells in the lungs and airways having decreased to near-normal le vels by 4 days. Plugs of mucus occluded some of the airways. These res ults indicate that some of the phenotypic changes in airway epithelium that follow an allergic response in the lung can be initiated before the migration of eosinophils or lymphocytes across the epithelial laye r.