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 exposure. The focus of this renewal will be the cellular, physiologic, and molecular mechanisms by which exposure 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 asthmatics 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 superimposed on the immune response to allergen exposure. Project 3 will address changes in the nervous components of the epithelial-mesenchymal trophic unit through two specific aims by establishing whether allergen and/or ozone exposure in neonates and adults alter. 1) structure and function of the airway neural allergen and/or ozone exposure in neonates and adults alter: 1) structure and function of the airway neural network including neurotransmission in the Nucleus Tractus Solitarious; 2) the role of airway neuroendocrine cells or neuroepithelial bodies in airway hyperresponsiveness. 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 or the repair phase.
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