A deficiency of pulmonary surfactant is known to be associated with respiratory distress syndrome (RDS) of the newborn, and is currently thought to be the primary cause of RDS. The functional agent in pulmonary surfactant is a lipid rich material, and most studies pertaining to the surfactant have been directed toward the investigation of its lipid moiety. However, there is increasingly strong evidence that pulmonary surfactant is actually a lipoprotein, containing specific apoproteins. This evidence has triggered, recently, an intense investigation about a possible role of apoproteins in surfactant synthesis, secretion, function and catabolism, and in the etiology and pathogenesis of RDS, as well as its treatment with artificial surfactants. Pulmonary surfactant isolated in several laboratories from the lungs of a number of animal species has been shown to contain a nonserum protein (38,000 daltons), which is believed to be the major surfactant apoprotein. In rat surfactant, we have identified 2 additional nonserum proteins (32,000 and 26,000 daltons), which appear to be related to the 38,000-dalton apoprotein. We propose, therefore, to characterize now the 3 proteins, of rat surfactant, and investigate if a precursor-product relationship exists among them and if one or all proteins are secreted with surfactant lipids. In order to delineate any difference(s) due to animal species, the 38,000-dalton protein of human surfactant will be also characterized. The following studies will be performed on surfactant apoproteins: 1) amino acid, carbohydrate and peptide analyses; 2) in vitro association with surfactant lipids; 3) determination of possible associated enzyme activity; and 4) in vivo incorporation of radiolabeled amino acids and choline into surfactant apoprotein and lipids, respectively. We propose, then, to develop an enzyme-linked immunoassay for the quantitation of the 38,000-dalton apoprotein in human amniotic fluid. The efficacy of the immunoassay, as a tool for predicting respiratory distress syndrome in the newborn, will be compared to that of existing methods based on analysis of lipids in amniotic fluid. With these studies, we hope to establish the specificity of the apoprotein(s), to gain an insight into possible functional role(s), and to explore their possible usefulness for diagnostic purposes.
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