Project: Research project

Project Details


Structural immaturity and deficiency of surfactant in the fetal lung cause the respiratory distress syndrome, the major factor contributing to neonatal death. Although surfactant replacement therapy reduces morbidity and mortality, it does not represent a cure for RDS. The cellular fate and metabolism of exogenous surfactant are unknown. Thus, understanding the mechanisms of cellular trafficking and reuptake in the developing fetal lung are crucial now that the use of exogenous surfactant therapy has become widespread. Reuptake of surfactant by adult type II epithelial cells is energy dependent and probably occurs via receptor-mediated endocytosis. Reuptake is enhanced by the major surfactant-associated protein (SP-A), which specifically binds to type II cells with high affinity and saturability. This is a fundamental process in the clearance, metabolism and recycling or resecretion of surfactant. All of the in vitro work on surfactant reuptake has utilized type II cells isolated from adult lung. We have recently shown a developmental increase in the reuptake of liposomes by type II cells derived from fetal rat lung concurrent with morphologic differentiation. This proposal will study the cellular mechanisms involved in the regulation of the development of surfactant reuptake using cultures of fetal type II cells. The effects of SP-A on reuptake of labelled surfactant phospholipid will be examined in undifferentiated fetal, differentiated fetal and neonatal type II cells to determine if the developmental changes in reuptake are mediated by changes in the expression of SP-A or binding of SP-A to the cell surface. The effects of SP-A on the location of internalized surfactant phospholipid as a function of time will be studied using cell fractionation techniques. We then plan to isolate and purify the putative receptor using ligand affinity chromatography. Once the receptor is purified, monoclonal antibodies and other molecular probes, such as cDNA, will be generated to study the developmental regulation of the expression of the gene for this receptor. In addition, we will use ligand binding assays to determine if developmental differences in uptake are due to developmental changes in receptor capacity and/or affinity. Information from this project will be used in future studies of the regulation of the differentiation of the type II cell.
Effective start/end date7/1/936/30/96


  • National Heart, Lung, and Blood Institute: $103,801.00


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