Respiratory distress syndrome (RDS) of the newborn and adult respiratory distress syndrome (ARDS) are prevalent clinical disorders where either a deficiency of functional surfactant or its inactivation is a contributing factor to the associated pathophysiology and high mortality. Surfactant protein C (SP-C), a small hydrophobic, protein which co-isolates with the surfactant lipids both enhances biophysical activity and improves resistance to inactivation of surfactant phospholipid. Recently, advances have been made in understanding lung phospholipid metabolism; however, little is known about the metabolism of SP-C, in part due to extreme hydrophobicity of the peptide as well as the lack of specific anti-SP-C antibodies. This proposal seeks to investigate cellular and molecular mechanisms responsible for the metabolism of SP-C by the alveolar type II pneumocyte. Structurally, SP-C is unique among the surfactant proteins in that it contains a membrane spanning sequence and covalent lipid modification. From preliminary data, we hypothesize that metabolic pathways for SP-C production and recycling are distinct t from other surfactant proteins and phospholipids. Specifically we plan to: a) Evaluate synthesis and post-translational processing of SP-C; b) Examine the role of palmitoylation in SP-C processing; c) Evaluate reuptake pathways of SP-C from the alveolar space. Key technical features which are unique to this proposal include the development of a monospecific antibody against SP-C propeptides, methodology for performing binding studies with hydrophobic surfactant proteins, and availability of a well-characterized and reproducible isolated perfused lung model.
| Beers, M F; Kim, C Y; Dodia, C et al. (1994) Localization, synthesis, and processing of surfactant protein SP-C in rat lung analyzed by epitope-specific antipeptide antibodies. J Biol Chem 269:20318-28 |
