Congenital alveolar proteinosis due to surfactant protein B (SP-B) deficiency is a fatal respiratory disorder unresponsive to conventional therapies. The role of surfactant proteins in surfactant function and metabolism is not completely understood. The discovery of this deficiency offers a unique opportunity to investigate the role of SP-B in surfactant function and metabolism. The overall objective of this project is to obtain further knowledge of the alterations in alveolar surfactant from the lungs of SP-B deficient infants as well as probe the role of SP-B in surfactant function and metabolism. The first specific aim will assess the composition and functionality of SP-B deficient surfactant, including an analysis of alveolar surfactant and intracellular surfactant isolated from lung tissue. An analysis of the subtypes of surfactant forms on the alveolar surface will be made to assess the role of SP-B in alveolar surfactant processing. As measures to stabilize the respiratory function of SP-B deficient infants prior to lung transplant would be important, in vitro studies to determine if addition of specific surfactant components to the deficient surfactant will restore normal surface activity will be carried out.
The second aim examines abnormalities in the metabolism of surfactant in type II cells isolated from SP-B deficient lung tissue. This includes the development of methodology to cryopreserve type II cells following isolation from lung. Data presented suggest the cells may be used in culture without loss of function. Cells isolated from both SP-B deficient and normal age matched lungs will be used to determine the effect of the SP-B deficiency on the synthesis, secretion and reutilization of surfactant phospholipids, particularly phosphatidylglycerol, which is apparently decreased in SP-B deficiency and surfactant proteins. Studies on the effect of SP-B deficiency on the trafficking of lipids to the lamellar body will assess the role of the intracellular form of SP-B in this process. The results of these studies will add greatly to our knowledge of the function of SP-B and why its absence should lead to respiratory death.
| Beers, M F; Hamvas, A; Moxley, M A et al. (2000) Pulmonary surfactant metabolism in infants lacking surfactant protein B. Am J Respir Cell Mol Biol 22:380-91 |
