The goals of the proposed research are to study the characteristics and regulation of active and passive water and solute transport across the pulmonary alveolar epithelial barrier, and to understand their roles in alveolar homeostasis and edemagenesis. We will study these transport properties using two preparations of isolated alveolar epithelium, in addition to the intact epithelium of the perfused rat lung. The overall premise of our program is that information about the characteristics and regulation of the transport of water and solutes across alveolar epithelium will lead to further insight not only into the basic functions of this tissue barrier, but also into the importance of such transport properties in the generation and removal of alveolar fluid under normal and abnormal conditions. The investigations will follow a multi-pronged approach of utilizing the two isolated epithelial preparations (mammalian alveolar epithelial cells in primary culture, and the hollow lungs of amphibians) to generate fundamental information about transport across the alveolar epithelial barrier. Mammalian type Ii cells will be studied primarily as monolayers n porous surfaces, and amphibian lungs will be studied as sacs and flat sheets. Information generated in these basic investigations will be compared to that from studies of transport across the intact alveolar epithelium of the perfused mammalian lung. Specific studies of the passive transport properties of these preparations will include determination of passive solute permeabilities, water flux due to hydrostatic and/or osmotic pressure gradients, and pathways for transport across the alveolar epithelium. Active transport studies will include measurements of bioelectric properties (including spontaneous potential difference, tissue resistance and short circuit current), active ion (sodium) fluxes, and water movements due to active solute transport. Investigation of the effects of physiocochemical parameters (e.g., temperature, pH), pharmacological agents (e.g., hormones), and especially lung injury (e.g., by oxidants) constitute a major part of this proposal. It is anticipated that our investigations will provide further insight into the transport characteristics of the alveolar epithelial barrier in normal and abnormal adult mammalian lungs, and into the roles of these barrier properties in normal alveolar homeostasis and alveolar pulmonary edema in vivo.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL038578-02
Application #
3563705
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1986-09-01
Project End
1992-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Type
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065
Zhou, Beiyun; Liu, Yixin; Kahn, Michael et al. (2012) Interactions between ?-catenin and transforming growth factor-? signaling pathways mediate epithelial-mesenchymal transition and are dependent on the transcriptional co-activator cAMP-response element-binding protein (CREB)-binding protein (CBP). J Biol Chem 287:7026-38
Zhou, Beiyun; Buckley, Stephen T; Patel, Vipul et al. (2012) Troglitazone attenuates TGF-ýý1-induced EMT in alveolar epithelial cells via a PPARýý-independent mechanism. PLoS One 7:e38827
Yacobi, Nazanin R; Fazllolahi, Farnoosh; Kim, Yong Ho et al. (2011) Nanomaterial interactions with and trafficking across the lung alveolar epithelial barrier: implications for health effects of air-pollution particles. Air Qual Atmos Health 4:65-78
Fazlollahi, Farnoosh; Sipos, Arnold; Kim, Yong Ho et al. (2011) Translocation of PEGylated quantum dots across rat alveolar epithelial cell monolayers. Int J Nanomedicine 6:2849-57
Zhong, Qian; Zhou, Beiyun; Ann, David K et al. (2011) Role of endoplasmic reticulum stress in epithelial-mesenchymal transition of alveolar epithelial cells: effects of misfolded surfactant protein. Am J Respir Cell Mol Biol 45:498-509
Kim, Yong Ho; Fazlollahi, Farnoosh; Kennedy, Ian M et al. (2010) Alveolar epithelial cell injury due to zinc oxide nanoparticle exposure. Am J Respir Crit Care Med 182:1398-409
Yacobi, Nazanin R; Malmstadt, Noah; Fazlollahi, Farnoosh et al. (2010) Mechanisms of alveolar epithelial translocation of a defined population of nanoparticles. Am J Respir Cell Mol Biol 42:604-14
Flodby, Per; Borok, Zea; Banfalvi, Agnes et al. (2010) Directed expression of Cre in alveolar epithelial type 1 cells. Am J Respir Cell Mol Biol 43:173-8
Borok, Zea; Crandall, Edward D (2009) More life for a ""terminal"" cell. Am J Physiol Lung Cell Mol Physiol 297:L1042-4
Patel, Leena N; Wang, Jeffrey; Kim, Kwang-Jin et al. (2009) Conjugation with cationic cell-penetrating peptide increases pulmonary absorption of insulin. Mol Pharm 6:492-503

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