Research Project
3439974
It has become apparent recently that pulmonary surfactant phospholipid molecules move between functional compartments within the alveolar subphase of the lung, including extensive recycling of surfactant to the type II pneumocytes. Evidence has been obtained for the existence of a protein in the alveolar subphase that catalyzes the transfer of phospholipids between artificial membranes. The projects outlined in this proposal are directed at determining whether or not this protein is a normal secretory component of type II pneumocytes and whether or not this protein can catalyze the reincorporation of surfactant phospholipids back into the type II pneumocyte for recycling. Type II pneumocytes will be isolated from rat lungs using elastase. The cells in monolayer culture will be stimulated to secrete surfactant and the medium will be examined for phospholipid transfer activity. Other experiments will involve incubation of isolated type II pneumocytes in suspension culture with a purified phospholipid transfer protein from lavage material. Vesicles of various composition will be used as donor membranes and the nature and specificity of the transfer process to the type II pneumocyte determined. An elucidation of the mechanisms controlling the movement of phospholipids between the various functional compartments of the lung is essential to understanding and eventually manipulating the pulmonary surfactant system. A clear understanding of the role of alveolar subphase proteins may be required before a fully functional artificial surfactant can be developed.
