Formation of acidic phospholipids in rabbit lung during perinatal development.

Abstract

Summary: Phospholipids were measured in the lamellar bodies and alveolar lavage of perinatal rabbits. Between 28 and 31 fetal days, phosphatidylinositol (PI) increased, and phosphatidylserine decreased. Small amounts of phosphatidylglycerol (PG) appeared at term. After birth, PG markedly increased and PI concomitantly decreased. PG increased prematurely after removal from the uterus of fetuses 29 days gestation or more. Fatty acid analysis of PG and PI revealed the presence of 62 to 63%, and 58 to 59%, of saturated species, respectively. As measured in total lung homogenate, PI increased between 28 and 31 fetal days, and PG increased between term and the first neonatal day. Glycerol incorporation into PG increased at birth, according to the measurement of lung slices. myo-Inositol incorporation into PI increased in the fetus parallel to accumulation of surfactant. The development of the following enzyme activities was studied in subcellular fractions derived from lung homogenates: phosphatidate cytidyltransferase, cytidine 5′-diphosphate (CDP)-diglyceride:inositol transferase, glycerophosphate phosphatidyltransferase, and phosphatidylglycerophosphatase. As measured in the microsomal fraction, all the activities increased between 27 and 30 fetal days. Shortly after birth, phosphatidate cytidyltransferase and glycerophosphate phosphatidyltransferase increased further, whereas the two other enzyme activities decreased somewhat. Cytidine 5′-diphosphate diglyceride:inositol transferase increased after the newborn period. There were only small developmental changes in Km's. In contrast to microsomes, the mitochondrial activities mainly decreased during development. Phosphatidylglycerophosphatase was the only activity that was present in significant amounts in lamellar bodies. It is proposed that the developmental changes in the acidic surfactant phospholipids are due to changes in the biosynthesis rates in type II cell microsomes. This may be controlled both by changes in the enzyme activities (phosphatidate cytidyltransferase, cytidine 5′-diphosphate diglyceride:inositol transferase, and glycerophosphate phosphatidyltransferase) and by changes in substrate concentrations (myo-inositol and sn-glycerol-3-P). Speculation: Besides surfactant lecithin, phosphatidylglycerol is critical to alveolar stability and its absence may precipitate respiratory distress syndrome in the newborn. Surfactant phosphatidylglycerol and phosphatidylinositol serve as indices of fetal lung maturity or help to specify diagnosis of respiratory distress in the neonate. Because several hormones seem to regulate individual surfactant phospholipids, the measurement of these components (lung profile) could be a way to analyze consequences of hormonal or nutritional balance and eventually correct it if necessary.