This core will assess surfactant metabolism a and surfactant function in the normal and transgenic mouse models used for the projects. All techniques to be used in this Core have been previously published in studies using transgenic mice. Four techniques to be used in this core have been previously published in studies using transgenic mice. Four types of measurements of surfactant metabolism and function will be provided to the projects: 1. Metabolic measurements of surfactant in vivo will include a) pool sizes of saturated phosphatidylcholine (Sat PC) in alveolar lavage and lung tissue; b) phospholipid composition for selected studies; c) radiolabeled precursor incorporation into St PC and measurements of the kinetics of surfactant secretion; and d) clearance kinetics for radiolabeled surfactant components (Sat PC, SP-A, SP-B, SP-C) given by intratracheal injection. These measurements provide information on the flux of surfactant into and out of the alveolus. 2. The surface activity of surfactant will be evaluated in vitro by measurements of a) minimum and maximum surface tension: b) sensitivity of surface tension lowering properties of surfactant to inhibition by plasma protein; and c) absorption rate. The Wilhelmy balance and/or captive bubble surfactometer will be used for above measurements. 3. Surfactant function will be measured in vivo by giving surfactant isolated from alveolar laves of mice to be surfactant deficient 27 d gestation premature rabbits. The effects of the test surfactants on dynamic compliance during ventilation and static pressure volume curves of the premature rabbit lung will be quantified.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL061646-03
Application #
6459578
Study Section
Project Start
2001-07-01
Project End
2002-06-30
Budget Start
Budget End
Support Year
3
Fiscal Year
2001
Total Cost
$282,268
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
Whitsett, Jeffrey A; Weaver, Timothy E (2015) Alveolar development and disease. Am J Respir Cell Mol Biol 53:1-7
Conkright, Juliana J; Apsley, Karen S; Martin, Emily P et al. (2010) Nedd4-2-mediated ubiquitination facilitates processing of surfactant protein-C. Am J Respir Cell Mol Biol 42:181-9
Xu, Yan; Zhang, Minlu; Wang, Yanhua et al. (2010) A systems approach to mapping transcriptional networks controlling surfactant homeostasis. BMC Genomics 11:451
Suzuki, Takuji; Sakagami, Takuro; Young, Lisa R et al. (2010) Hereditary pulmonary alveolar proteinosis: pathogenesis, presentation, diagnosis, and therapy. Am J Respir Crit Care Med 182:1292-304
Hardie, William D; Hagood, James S; Dave, Vrushank et al. (2010) Signaling pathways in the epithelial origins of pulmonary fibrosis. Cell Cycle 9:2769-76
Whitsett, Jeffrey A; Wert, Susan E; Weaver, Timothy E (2010) Alveolar surfactant homeostasis and the pathogenesis of pulmonary disease. Annu Rev Med 61:105-19
Kramer, Elizabeth L; Mushaben, Elizabeth M; Pastura, Patricia A et al. (2009) Early growth response-1 suppresses epidermal growth factor receptor-mediated airway hyperresponsiveness and lung remodeling in mice. Am J Respir Cell Mol Biol 41:415-25
Wang, Mei; Bridges, James P; Na, Cheng-Lun et al. (2009) Meckel-Gruber syndrome protein MKS3 is required for endoplasmic reticulum-associated degradation of surfactant protein C. J Biol Chem 284:33377-83
Hardie, William D; Glasser, Stephan W; Hagood, James S (2009) Emerging concepts in the pathogenesis of lung fibrosis. Am J Pathol 175:3-16
Korfhagen, Thomas R; Le Cras, Timothy D; Davidson, Cynthia R et al. (2009) Rapamycin prevents transforming growth factor-alpha-induced pulmonary fibrosis. Am J Respir Cell Mol Biol 41:562-72

Showing the most recent 10 out of 91 publications