This project is designed to explore the mechanisms involved in the pathogenesis of pulmonary alveolar proteinosis, a disease characterized by the accumulation of lipoproteineous material within the airways. Previous studies have demonstrated profound defects in phagocytosis in alveolar macrophages that appear """"""""overfed"""""""" with lipoproteinaceous debri (1). However, studies of surfactant metabolism convincingly show that alveolar macrophages play only a minor role in surfactant turnover under normal circumstances, which is instead re-utilized by type Ii epithelial cells after secretion (2). In this project, studies will be conducted of the morphological and biochemical features of rat alveolar machrophages and type II epithelial cells in culture. They will include studies of the fate and distribution of 5'-nucleotidase in macrophages and type II epithelial cells as a probe of membrane events during endocytosis. Next the uptake and distribution of flourescent phospholipid analogues will be analyzed in colocalization experiments with 5'-nucleotidase and antibodies directed against lysosomes and golgi complex. Alterations in the uptake and distribution of flourescent phospholipid analogues in type II cells will be analyzed in drug-induced phospholipidosis in rats. And finally, the uptake, distribution, and secretion of flourescently labeled phospholipids by type II cells will be analyzed in colocalization experiments with 5'-nucleotidase and antibodies directed against golgi complex and lysosomes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Physician Scientist Award (K11)
Project #
5K11HL001963-03
Application #
3087453
Study Section
Research Manpower Review Committee (MR)
Project Start
1987-07-01
Project End
1992-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Gibson, K F; Phadke, S (1994) Intracellular distribution of lysozyme in rat alveolar type II epithelial cells. Exp Lung Res 20:595-611
Gibson, K F; Widnell, C C (1991) The relationship between lamellar bodies and lysosomes in type II pneumocytes. Am J Respir Cell Mol Biol 4:504-13