The specific aims of the proposed research are: 1) To purify two partially characterized phospholipid transfer proteins from lung. 2) To establish the molecular characteristics of these unique proteins. 3) to delineate those factors important for the functional activity and specificity of the transfer of phospholipids. 4) To develop a monoclonal antibody specific for each of the two proteins. 5) To describe the developmental pattern of these phospholipid transfer proteins from fetal to adult life. The methods for initial purification of the proteins will be those of classical protein chemistry. The small amounts of protein purified in this manner will be used to produce a specific monoclonal antibody. Purification of larger amounts of the transfer proteins will then be possible using immunoadsorbent chromatography. Membrane fluidity (using artificial phospholipid vesicles and natural membranes) will be studied extensively to determine the importance of this variable in the rates of phospholipid transfer by these proteins. The monoclonal antibodies will be prepared using the recently developed mouse myeloma-hybridoma techniques. Availability of these specific antibodies provide powerful tools to monitor the concentrations of the phospholipid exchange proteins in developmental and disease models. The long-term objective of this research is to provide a better understanding of membrane biogenesis in general and lamellar body biogenesis in Type II pneumocytes in particular. This information will provide a better understanding of the physiology of pulmonary function and of the biochemical control of surfactant production. Insight into the problems of respiratory distress syndrome and other pulmonary diseases in both children and adults from the data accumulated in these studies can lead to strategies for better clinical management of these patients.
| Funkhouser, J D (1987) Amino-terminal sequence of a phospholipid transfer protein from rat lung. Biochem Biophys Res Commun 145:1310-4 |
| Funkhouser, J D; Cheshire, L B; Read, R J et al. (1987) Monoclonal antibody isolation of type II pneumocytes. Cytometry 8:321-6 |
| Funkhouser, J D; Cheshire, L B; Ferrara, T B et al. (1987) Monoclonal antibody identification of a type II alveolar epithelial cell antigen and expression of the antigen during lung development. Dev Biol 119:190-8 |
| Funkhouser, J D; Read, R J (1985) Phospholipid transfer proteins from lung, properties and possible physiological functions. Chem Phys Lipids 38:17-27 |
