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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
2P01ES000628-27A1
Application #
6361664
Study Section
Special Emphasis Panel (ZES1-EBJ-A (P1))
Project Start
1978-09-30
Project End
2005-06-30
Budget Start
Budget End
Support Year
27
Fiscal Year
2000
Total Cost
$157,209
Indirect Cost
Name
University of California Davis
Department
Type
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Crowley, Candace M; Fontaine, Justin H; Gerriets, Joan E et al. (2017) Early life allergen and air pollutant exposures alter longitudinal blood immune profiles in infant rhesus monkeys. Toxicol Appl Pharmacol 328:60-69
Hsia, Connie C W; Hyde, Dallas M; Weibel, Ewald R (2016) Lung Structure and the Intrinsic Challenges of Gas Exchange. Compr Physiol 6:827-95
Herring, Matt J; Avdalovic, Mark V; Lasley, Bill et al. (2016) Elderly Female Rhesus Macaques Preserve Lung Alveoli With Estrogen/Progesterone Therapy. Anat Rec (Hoboken) 299:973-8
Lynn, Therese M; Molloy, Emer L; Masterson, Joanne C et al. (2016) SMAD Signaling in the Airways of Healthy Rhesus Macaques versus Rhesus Macaques with Asthma Highlights a Relationship Between Inflammation and Bone Morphogenetic Proteins. Am J Respir Cell Mol Biol 54:562-73
Herring, M J; Putney, L F; St George, J A et al. (2015) Early life exposure to allergen and ozone results in altered development in adolescent rhesus macaque lungs. Toxicol Appl Pharmacol 283:35-41
Van Winkle, Laura S; Bein, Keith; Anderson, Donald et al. (2015) Biological dose response to PM2.5: effect of particle extraction method on platelet and lung responses. Toxicol Sci 143:349-59
Madl, Amy K; Plummer, Laurel E; Carosino, Christopher et al. (2014) Nanoparticles, lung injury, and the role of oxidant stress. Annu Rev Physiol 76:447-65
Herring, Matt J; Putney, Lei F; Wyatt, Gregory et al. (2014) Growth of alveoli during postnatal development in humans based on stereological estimation. Am J Physiol Lung Cell Mol Physiol 307:L338-44
Moore, Brian D; Hyde, Dallas M; Miller, Lisa A et al. (2014) Persistence of serotonergic enhancement of airway response in a model of childhood asthma. Am J Respir Cell Mol Biol 51:77-85
Murphy, Shannon R; Oslund, Karen L; Hyde, Dallas M et al. (2014) Ozone-induced airway epithelial cell death, the neurokinin-1 receptor pathway, and the postnatal developing lung. Am J Physiol Lung Cell Mol Physiol 307:L471-81

Showing the most recent 10 out of 62 publications