The turnover of surfactant phospholipid by the lung epithelium is proving to be a much more active process than was previously thought. It is hypothesized that the hydrophobic low molecular weight surfactant apoproteins play a role in the regulation of this surfactant re-uptake by the lung alveolar epithelium. Using modifications of previously published techniques, I have isolated and purified a group of hydrophobic apoproteins from rat lung surfactant. I demonstrate that these proteins appear to augment the uptake of radioactive liposomes by isolated Type II pneumocytes in primary culture. I propose to further define the conditions of these protein-lipid-cell interactions, to explore the mechanism of protein augmented liposome uptake by Type II cells, and to examine the nature of the Type II cell-hydrophobic protein interaction. By radiolabelling the hydrophobic proteins, I will attempt to define the receptor kinetics of the potential cell-protein interactions and protein-receptor internalization in cultured Type II cells. I will also characterize hydrophobic proteins from normal human lungs and compare them to the proteins recovered from the lung lavage material of patients with the surfactant disorder of Pulmonary Alveolar Lipo-Proteinosis. I will examine the uptake of liposomes in a perfused lung system to asses the effects of the hydrophobic proteins on the whole organ uptake to liposomal phospholipid. In summary, I hope to fully examine the role of the hydrophobic proteins as a regulator of normal surfactant reprocessing and to investigate the protein's possible role in the pathophysiology of the human lung disorder Pulmonary Alveolar Lipo-Proteinosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL001537-03
Application #
3081900
Study Section
(SRC)
Project Start
1984-07-01
Project End
1988-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Schools of Medicine
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Wolf, K M; Mehta, D; Claypool, W D (1988) Mucoepidermoid carcinoma of the lung with intracranial metastases. Chest 94:435-8