Lung disease, which affects more than 34 million Americans, is physically and psychologically distressing. Cigarette smoke induced injury contributes to a large number of diseases and is the primary cause of lung disease. However, the mechanisms by which cigarette smoke induced injury causes disease have not been fully elucidated. Studies suggest in utero exposure to cigarette smoke results in small for gestational age infants and correlates with increased risk for sudden infant death syndrome and asthma. In addition, findings from a recent study suggest cigarette smoking causes cellular aging (telomere shortening). Perhaps cigarette smoking or secondary cigarette smoke induces cell aging in the young and predisposes children to the development of lung disease. This issue has not yet been systematically explored. The long term goal of the proposed work is to prevent physical and psychological distress and ultimately death from lung disease. The purpose of this proposed research is to learn more about the impact of cigarette smoke induced injury by performing studies on pulmonary alveolar and endothelial cells derived from neonatal, young, and old rats used to construct cell culture models.
SPECIFIC AIM 1 is to develop culture models to study cigarette smoke induced injury in alveolar and pulmonary endothelial cells. Alveolar and microvascular endothelial cells from the lung (MVECL) isolated from neonatal, young, and old rats will be cultured separately. Then alveolar and MVECL isolated from neonatal, young, and old rats will be co-cultured to mimic the alveolus of the lung.
SPECIFIC AIM 2 is to quantify and compare levels of reactive oxygen species (ROS) in alveolar and MVECL isolated from neonatal, young, and old rats with and without exposure to cigarette smoke extract (CSE).
SPECIFIC AIM 3 is to quantify and compare markers of cigarette smoke induced injury (telomere length, senescence, and apoptosis) in alveolar and MVECL isolated from neonatal, young, and old rats with and without exposure to CSE.
SPECIFIC AIM 4 is to quantify and compare levels of markers of endothelial dysfunction in MVECL isolated from neonatal, young, and old rats with and without exposure to CSE. P-selectin and nitric oxide will be examined as markers of endothelial dysfunction.
The aims will be achieved by using cell culture models and a variety of biochemical and microscopy techniques. A better understanding of the effects of cigarette smoke induced injury on alveolar cells and MVECL of different ages will begin to provide necessary information to develop tailored educational, diagnostic, and treatment regimens to combat physically and psychologically distressing lung disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NR010843-03
Application #
7790677
Study Section
National Institute of Nursing Research Initial Review Group (NRRC)
Program Officer
Banks, David
Project Start
2008-04-01
Project End
2011-08-01
Budget Start
2010-04-01
Budget End
2011-08-01
Support Year
3
Fiscal Year
2010
Total Cost
$37,185
Indirect Cost
Name
University of Arizona
Department
Type
Schools of Nursing
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
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Downs, Charles A; Montgomery, David W; Merkle, Carrie J (2011) Age-related differences in cigarette smoke extract-induced H2O2 production by lung endothelial cells. Microvasc Res 82:311-7
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