Ozone is the principal oxidant air pollutant in most American cities. Our program has established that the pathobiologic response of the mammalian respiratory system to inhalation of ambient concentrations of ozone of ozone focuses on the epithelium and varies by species, position within the airway tree and duration of exposure. The focus of this renewal will be the cellular, physiologic, and molecular mechanisms by which exposures to oxidant air pollutants, in concern with allergens, contributes to the development of asthma. The overall hypothesis being tested is that the episodic nature of environmental exposure to oxidant air pollutants: a) promotes the development of asthma and exacerbates the allergen response in asthmatic by altering the homeostasis of the airway epithelial- mesenchymal trophic unit in adults; and b) elevates the severity of asthma in the young by fundamentally altering the postnatal development of these trophic interactions These changes result from continual cycles of acute injury, inflammation and repair superimposed on the immune response to allergen exposure. Project 1 will address changes in the epithelial and mesenchymal compartments of the trophic unit through three specific aims by defining the response to allergen-induced asthma and/or ozone exposure in: 1) the epithelial compartment; 2) cells and matrix in the allergen-induced asthma and/or ozone exposure in: 1) the epithelial compartment; 2) cells and matrix in the mesenchymal compartment; 3) antioxidant concentrations in the epithelial compartment and extracellular airway lining fluid; 3) anti-oxidant concentrations in the epithelial compartment and extracellular airway lining fluid. All three projects will compare responses in the same neonatal and adult rhesus monkeys following episodic exposure to ozone and repeated challenge with a human allergen, house dust mite, during either the injury/inflammation phase of ozone exposure of the repair phase.
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