and Specific Aims.) Intercellular adhesion molecule-1 (ICAM-1) is a cell surface adhesion protein that plays an important role for lymphocyte and monocyte adherence and migration and is involved in the transduction of critical co-stimulatory signals for the activation of T cells. The overall goal of the application is to elucidate the regulation of ICAM-1 expression in alveolar epithelial cells in vitro. To accomplish this objective, experiments will be performed examining primary cultures of rat cells isolated as type II epithelial cells which undergo in vitro differentiation towards the type I cell phenotype.
Specific Aim I will delineate the roles of a selected set of signals that may be involved in the control of alveolar epithelial cell ICAM-1 expression.
Specific Aim 2 will investigate the molecular biology of ICAM-1 regulation in alveolar epithelial cells, focusing of the roles of protein and mRNA turnover, and initiation and elongation of mRNA transcription. In addition, data suggest that ICAM-1 is associated with cytoskeletal elements, and the functional activity of ICAM-1 may depend on the interaction with the cytoskeleton.
Specific Aim 3 will determine the nature and regulation of this interaction between ICAM-1 and the cytoskeleton. Thus this project proposes to define the regulation of alveolar epithelial ICAM-1 expression from the initiation of transcription of the gene to the macromolecular associations at the cell surface. The work may provide insights into the regulation of epithelial cell differentiation in the alveolar space and may provide insights into the expression of a molecule which may play a critical role in defining the immunologic milieu of the alveolar space.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL050496-02
Application #
2226715
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1993-08-01
Project End
1997-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Brock, Thomas G; Peters-Golden, Marc (2007) Activation and regulation of cellular eicosanoid biosynthesis. ScientificWorldJournal 7:1273-84
Luo, Ming; Jones, Sandra M; Flamand, Nicolas et al. (2005) Phosphorylation by protein kinase a inhibits nuclear import of 5-lipoxygenase. J Biol Chem 280:40609-16
Brock, Thomas G; Lee, Young-Jik; Maydanski, Elana et al. (2005) Nuclear localization of leukotriene A4 hydrolase in type II alveolar epithelial cells in normal and fibrotic lung. Am J Physiol Lung Cell Mol Physiol 289:L224-32
Luo, Ming; Jones, Sandra M; Phare, Susan M et al. (2004) Protein kinase A inhibits leukotriene synthesis by phosphorylation of 5-lipoxygenase on serine 523. J Biol Chem 279:41512-20
Luo, Ming; Jones, Sandra M; Peters-Golden, Marc et al. (2003) Nuclear localization of 5-lipoxygenase as a determinant of leukotriene B4 synthetic capacity. Proc Natl Acad Sci U S A 100:12165-70
Beck, James M; Preston, Angela M; Wilcoxen, Steven E et al. (2003) Pneumocystis pneumonia increases the susceptibility of mice to sublethal hyperoxia. Infect Immun 71:5970-8
Brock, Thomas G; McNish, Robert W; Mancuso, Peter et al. (2003) Prolonged lipopolysaccharide inhibits leukotriene synthesis in peritoneal macrophages: mediation by nitric oxide and prostaglandins. Prostaglandins Other Lipid Mediat 71:131-45
Brock, T G; Maydanski, E; McNish, R W et al. (2001) Co-localization of leukotriene a4 hydrolase with 5-lipoxygenase in nuclei of alveolar macrophages and rat basophilic leukemia cells but not neutrophils. J Biol Chem 276:35071-7
Christensen, P J; Bailie, M B; Goodman, R E et al. (2000) Role of diminished epithelial GM-CSF in the pathogenesis of bleomycin-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 279:L487-95

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