Studies of catabolism and turnover of surfactant indicate that significant amounts of-surfactant lipids are reutilized by type II cells by an efficient recycling process. The goal of this project is to elucidate the mechanisms involved. Understanding the recycling mechanism is important in optimizing techniques for surfactant replacement therapy and will provide basic information about the biochemistry of the regulation of surfactant content of lung alveoli. The hypothesis to be tested is that the uptake of phospholipids is a receptor-mediated process of the general type that is known to be involved in specific uptake of lipids by other types of cells, i.e., uptake of lipids and cholesterol by fibroblasts and uptake of lipoproteins and acetylated lipoproteins by macrophages and endothelial cells. The hypothesis is that known surfactant apoproteins or other proteins provide the specificity for uptake and redistribution of phospholipids by the cells.
The specific aims are the following: 1. Develop an in vitro system for studying recycling of surfactant phospholipids by type II epithelial cells and use the system to optimize the conditions for the specific uptake of dipalmitoyl phosphatidylcholine and sorting into lamellar bodies of the type II cells, 2. Determine whether surfactant apoproteins are taken up with the phospholipids and how incorporation of the different apoproteins into phospholipid preparations influences the structure of the phospholipid vesicles, their uptake and intracellular distribution. 3. Investigate the recycling process in terms of internalization mechanisms and intracellular pathways involved and determine whether an uptake process specific to type II cells can be demonstrated. 4. Determine whether uptake of exogenous phospholipids mediates physiological events in the cell such as changes in the phospholipid content or in the activity of enzymes involved in phospholipid biosynthesis or remodeling, 5. Investigate a possible role of phospholipid transfer proteins in the uptake of surfactant phospholipid and intracellular sorting of phospholipid components. 6. Investigate type II cell membrane proteins to determine if a protein with properties of a biological receptor for surfactant apoproteins can be identified.
| Jiang, X; Tangada, S; Peterson, R D et al. (1992) Expression of aminopeptidase N in fetal rat lung during development. Am J Physiol 263:L460-5 |
| Funkhouser, J D; Tangada, S D; Jones, M et al. (1991) p146 type II alveolar epithelial cell antigen is identical to aminopeptidase N. Am J Physiol 260:L274-9 |
| Funkhouser, J D; Tangada, S D; Peterson, R D (1991) Ectopeptidases of alveolar epithelium: candidates for roles in alveolar regulatory mechanisms. Am J Physiol 260:L381-5 |
