Regulation of the Lipid Composition of Lung Surfactant

Summary

During lung development, the phosphatidylinositol (PI)-rich surfactant that is produced by type II pneumonocytes of immature lungs is replaced by the phosphatidylglycerol (PG)-rich surfactant that is characteristic of mature lungs. Synthesis of phosphatidyicholine (PC) (the most abundant lipid of surfactant) increases before the change in the relative amounts of PG and PI and was found to be accompanied by an increase in the intracellular amount of CMP. CMP-dependent synthesis of PG in lung was demonstrated and its characteristics were consistent with the proposition that CMP promotes the reverse reaction catalyzed by PI synthase (EC 2.7.8.11) thus decreasing net synthesis of PI and increasing the availability of CDP-diacylglycerol for PG synthesis. When the amount of CMP in isolated type II pneumonocytes was increased, directly or indirectly, synthesis of PG was increased. Synthesis of PG by these cells was also influenced by extracellular myo-inositol at concentrations similar to those found in fetal serum. Availability of myo-inositol to lungs, from either synthesis in situ or uptake from the blood, was found to decline in late gestation. This developmental decline in myo-inositol availability is delayed in pregnancies that are complicated by diabetes mellitus and this may account for the delayed appearance of PG-rich fetal lung surfactant during such pregnancies.