CALCIUM-DEPENDENT PHOSPHOLIPID-BINDING PROTEINS AS RELATED TO LUNG DEVELOPMENT

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Bronchopulmonary dysplasia is the major sequela of respiratory distress syndrome (RDS) premature infants. Although it is clear that RDS is mainly due to the deficiency of lung surfactant, the mechanisms of the development of BPD remain poorly defined. Recently, we purified two Ca2+ - dependent phospholipid binding proteins (PLBPs) from rabbit lung. These proteins are found in alveolar type II cells and the lining layers of alveoli and larger airways, and they preferentially fuse vesicles to surfactant membranes. Our observations suggest that PLBPs may play an important role in surfactant biogenesis. Thus, if there is any deficiency of these proteins in lung, this may be associated with the development of RDS and/or BPD. These hypotheses will be tested by the following proposed experiments: (1) determine PLBPs in developing lungs and investigate the effects of steroids and hyperoxia on these proteins during lung growth; (2) investigate the relationship between PLBPs and the development of RDS and BPD; (3) study in vitro protein synthesis and post-translation modifications of PLBPs for better understanding the structure-function relationships of these proteins; (4) investigate the role and regulation of PLBPs in type II cells in relationship to surfactant metabolism; (5) study the mechanisms of binding of PLBPs with Ca2+, phospholipids and surfactant membranes for better understanding the protein's binding actions and the protein's preferential binding with surfactant membranes. These studies will provide important information for understanding the relationship between lung PLBPS, surfactant biogenesis and the development of RDS and BPD. Data from these studies may also prove useful for designing novel treatment for RDS and BPD.