Viral respiratory infections early in life may represent a significant risk factor for the development of asthma and for sensitization to common allergens during childhood. The mechanisms by which viral infections may render airways vulnerable to subsequent allergen exposure and the potential role of eosinophils in these processes are incompletely understood. In Brown Norway rats, viral bronchiolitis during a critical developmental period (3-4 weeks of life) induces a heightened state of airway vulnerability to the pathophysiological consequences of allergen sensitization and airway allergen exposure. These observations provide a rationale for using this rat model to test the hypothesis that the interaction of eosinophils with the post-viral airway environment may result in alterations in pulmonary function. There are at least two mechanisms, which are not mutually exclusive, that could account for an enhanced vulnerability of post-viral airways to eosinophil-dependent effects. First, eosinophils may experience changes in their phenotypic characteristics arising from migration into, and interactions with, the altered post-viral airways. Second, structural changes in the post-viral airway environment may increase the likelihood that eosinophils will migrate into and remain in the airway walls. Therefore, studies will be performed to track the migration of labeled eosinophils (which are either instilled into the airspace of the lung or infused intravenously) into normal and post-viral airways. The physiological consequences that occur as a result of the presence of these eosinophils in the airway walls will be determined using pulmonary function measurements and lung imaging techniques. The effect of IL-5 priming of these eosinophils, with or without activation by a secondary stimulus, on migration, granular protein release, and pulmonary physiology will be determined. These studies should provide important insights into mechanisms by which airway injury early in life may enhance the susceptibility of children to morbidity from aeroallergen sensitization and exposure.
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