MR Imaging of Excised Lung Tissue
EMSL Project ID
10193
Abstract
This project takes it basis from the dramatic remodeling produced in immature airways of infants monkeys (30 days-old) exposed cyclically to ozone and/or allergen for a prolonged period (5 months) of time during early postnatal lung growth. These unexpected findings have raised a number of fundamental questions regarding mechanisms by which: 1) the cellular and metabolic organization of conducting airways in adults is established in infants during the early postnatal period; 2) acute inflammation associated with exposure to oxidant air pollutants perturbs and resets developmental processes; 3) immune responses associated with exposure to allergen perturb and reset the developmental process separate from the impact of oxidants; 4) repeated cycles of exposure remodel the airway to establish conditions characteristic of the airways in asthmatic adults and children. This project will provide the basic data for the development of a dynamic model of airway growth and development as it impacts on susceptibility of infants and young children to growth altering exposures to air pollutants allergens.The overall hypothesis that we will test is that the following four characteristics of immature airways contribute to the heightened susceptibility of infants to oxidant exposure: 1) immature airway geometry and cellular organization; 2) alterations in O3 deposition patterns during postnatal growth; 3) local differences in levels of cellular and extracellular antioxidants and 4) airway specific differences in ability to generate an inflammatory response. We hypothesize that these factors are altered in a model of childhood allergic asthma and resulting in modulation of the O3 injury pattern rendering children more susceptible to environmental oxidant toxicity. This hypothesis will be tested by the following specific aims:
Specific Aim 1: Define age differences in the site specific pattern of injury following acute episodes of O3 exposure in relation to immature airway geometry and cellular organization, O3 deposition, site-specific levels of cellular and extracellular antioxidants and airway inflammation.
Hypothesis: Immature airway geometry and cellular organization and levels of cellular and extracellular antioxidants change in immature airways from early in postnatal development (30 days of age) to late in postnatal development (180 days of age) and these changes alter the deposition of O3 and the pattern of injury and inflammation following an acute O3 exposure.
Specific Aim 2: Define the site-specific pattern of injury following repeated episodes to O3 exposure in relation to immature airway geometry and cellular organization, O3 deposition, site-specific levels of cellular and extracellular antioxidants and airway inflammation.
Hypothesis: The cycle of injury and repair during repeated exposure to O3 during postnatal development alters immature airway geometry and cellular organization, O3 deposition and cellular and extracellular antioxidants levels resulting in more extensive and severe injury.
Project Details
Project type
Capability Research
Start Date
2004-12-30
End Date
2005-09-30
Status
Closed
Released Data Link
Team
Principal Investigator