Abstract

This proposal has as its goal the development and characterization of new nonsurfactant related markers of pulmonary alveolar type 2 and type 1 cells and the use of these markers to explore the in vitro and in vivo biology of the alveolar epithelium. The cell surface binding of sugar specific lectins and a newly described monoclonal antibody will be evaluated in the intact lung. This information will be transfered to isolated type 2 cells whose differentiated cell profile as defined by lectin binding, surfactant and matrix secretory products and ultrastructure will be characterized. The change of this profile with time in culture will be studied and a similar cell profile of the flat alveolar type 1-like cell will be defined. In vitro modulators of this time related change e.g. cell shape, matrix and media additives will be evaluated in order to develop insights into the factors which influence type 2 cell maturation or transition in vitro. Maturation and transition related lectin binding glycoproteins will be identified, isolated and used to raise monoclonal antibodies to cell specific antigens. These antibodies as well as other markers of cell differentiation will then be applied to several in vivo settings which are characterized by type 2 cell maturation or type 2 cell transition to type 1 cells in order to test the validity of the non-surfactant markers of cell differentiation. These studies should provide new cell specific markers of differentiated alveolar type 2 and type 1 cells which can be used to further explore the biology of these cells and provide insights into ways of influencing their state of differentiation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL034768-02
Application #
3348075
Study Section
Pathology A Study Section (PTHA)
Project Start
1985-07-15
Project End
1990-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118

  Publications

Panchenko, M P; Joyce-Brady, M; Starikova, M G et al. (1998) Atrial natriuretic peptide modulates alveolar type 2 cell adenylyl and guanylyl cyclases and inhibits surfactant secretion. Biochim Biophys Acta 1403:115-25
Cardoso, W V; Itoh, A; Nogawa, H et al. (1997) FGF-1 and FGF-7 induce distinct patterns of growth and differentiation in embryonic lung epithelium. Dev Dyn 208:398-405
Cardoso, W V; Mitsialis, S A; Brody, J S et al. (1996) Retinoic acid alters the expression of pattern-related genes in the developing rat lung. Dev Dyn 207:47-59
Maitre, B; Clement, A; Williams, M C et al. (1995) Expression of insulin-like growth factor receptors 1 and 2 in the developing lung and their relation to epithelial cell differentiation. Am J Respir Cell Mol Biol 13:262-70
Cardoso, W V (1995) Transcription factors and pattern formation in the developing lung. Am J Physiol 269:L429-42
Cardoso, W V; Williams, M C; Mitsialis, S A et al. (1995) Retinoic acid induces changes in the pattern of airway branching and alters epithelial cell differentiation in the developing lung in vitro. Am J Respir Cell Mol Biol 12:464-76
Clement, A; Edeas, M; Chadelat, K et al. (1992) Inhibition of lung epithelial cell proliferation by hyperoxia. Posttranscriptional regulation of proliferation-related genes. J Clin Invest 90:1812-8
Brody, J S; Williams, M C (1992) Pulmonary alveolar epithelial cell differentiation. Annu Rev Physiol 54:351-71
Clement, A; Steele, M P; Brody, J S et al. (1991) SV40T-immortalized lung alveolar epithelial cells display post-transcriptional regulation of proliferation-related genes. Exp Cell Res 196:198-205
Clement, A; Riedel, N; Brody, J S (1990) [3H]thymidine incorporation does not correlate with growth state in cultured alveolar type II cells. Am J Respir Cell Mol Biol 3:159-64

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