Respiratory ailments are responsible for a significant number of general practitioner (approximately 25 percent) and hospital (approximately 30 percent) visits each year. Many of these ailments are rooting in the dysfunctional cellular physiology of alveolar type II cells. Alveolar type II cells are epithelial cells that contribute to the lining of the lung. Among other things, these cells provide critical secretions in the lung that keep the lung from collapsing and provide for a proper aqueous environment that allows for proper oxygen exchange. Just as importantly, alveolar cells are crucial in general maintenance of the cellular layer following insult or injury. Dysfunction of alveolar II cells, as seen after severe cases of asthma, chronic bronchitis, bronchiectasis, infection or injury, can have serious effects on lung physiology, (e.g. reduced O2 transfer, altered liquid interface, or misplacement of cell types at the lung surface that further exasperate the diseased state). At any given time, there are tens to hundreds of thousands of alveolar II cells working together to maintain lung homeostasis. However, there is little known concerning the cellular mechanisms that allow for alveolar cells work together for normal lung function. It is the purpose of this proposal to utilize advanced microscopy techniques that allows us to monitor communication pathways between cells and discover how alveolar cells coordinate their function. It is essential that we understand the basic cellular processes that lead to communicated and coordinated tissue and organ outcomes. With a model system for alveolar intercellular communication could expedite the formulating and testing of new medical treatments for dysfunctional alveolar cell physiology that underlies specific airway conditions following disease, insult and injury in the lung.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15HL064636-01
Application #
6085049
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
2000-03-01
Project End
2002-02-28
Budget Start
2000-03-01
Budget End
2002-02-28
Support Year
1
Fiscal Year
2000
Total Cost
$135,386
Indirect Cost
Name
University of Wyoming
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
069690956
City
Laramie
State
WY
Country
United States
Zip Code
82071
Isakson, Brant E; Olsen, Colin E; Boitano, Scott (2006) Laminin-332 alters connexin profile, dye coupling and intercellular Ca2+ waves in ciliated tracheal epithelial cells. Respir Res 7:105
Olsen, Colin O; Isakson, Brant E; Seedorf, Gregory J et al. (2005) Extracellular matrix-driven alveolar epithelial cell differentiation in vitro. Exp Lung Res 31:461-82
Isakson, Brant E; Seedorf, Gregory J; Lubman, Richard L et al. (2003) Cell-cell communication in heterocellular cultures of alveolar epithelial cells. Am J Respir Cell Mol Biol 29:552-61
Groathouse, Nathan A; Heinzen, Robert A; Boitano, Scott (2003) Functional BvgAS virulence control system in Bordetella bronchiseptica is necessary for induction of Ca2+ transients in ciliated tracheal epithelial cells. Infect Immun 71:7208-10
Isakson, Brant E; Seedorf, Gregory J; Lubman, Richard L et al. (2002) Heterocellular cultures of pulmonary alveolar epithelial cells grown on laminin-5 supplemented matrix. In Vitro Cell Dev Biol Anim 38:443-9
Isakson, B E; Lubman, R L; Seedorf, G J et al. (2001) Modulation of pulmonary alveolar type II cell phenotype and communication by extracellular matrix and KGF. Am J Physiol Cell Physiol 281:C1291-9
Isakson, B E; Evans, W H; Boitano, S (2001) Intercellular Ca2+ signaling in alveolar epithelial cells through gap junctions and by extracellular ATP. Am J Physiol Lung Cell Mol Physiol 280:L221-8