Structure and function of phosphatidylglycerol-deficient lung surfactant.

Abstract

The structure and properties of phosphatidylglycerol-deficient lung surfactant were examined using the myoinositol-treated rat as an experimental model. Hyperinositolemia was produced in pregnant rats (and their fetuses) by the administration of myoinositol throughout the final 5 days of gestation. Weight gain by pregnant rats during this period was reduced significantly as a result of myoinositol treatment. On day 21 of gestation, the number of type II cells in sections of lungs from fetuses of myoinositol-treated rats was not significantly different from that of fetuses of saline-treated rats. The profile area occupied by lamellar bodies, however, was significantly decreased in type II cells of fetuses from myoinositol-treated rats. There also was an apparent decrease in the size of lamellar bodies in the lungs of hyperinositolemic fetuses, but this was not accompanied by alterations in the structure of the tubular myelin form of surfactant present in fetal alveoli. Nonpregnant adult rats treated with myoinositol exhibited no gross respiratory impairment, and the recovery of total phospholipid in their alveolar lavage fluid was indistinguishable from that of saline-treated rats. In contrast, the phosphatidylglycerol content of the lavage fluid was decreased and the phosphatidylinositol content was increased as a result of myoinositol treatment. Furthermore, the molar ratio of palmitate to stearate esterified in phosphatidylglycerol was decreased (from 6.2 to 1.4) after myoinositol treatment. The palmitate/stearate ratio for phosphatidylinositol, however, tended to increase after myoinositol treatment. Pressure-volume relationships for freshly excised lungs of myoinositol-treated rats were not significantly different from those for lungs of saline-treated rats. Similarly, the surface-active properties of phosphatidylglycerol-deficient surfactant, measured in vitro by use of a surface balance, were not different from those of normal surfactant. These data indicate that phosphatidylglycerol-deficient surfactant has normal surface activity, and that the apparent requirement for phosphatidyglycerol for normal respiration in the neonate is likely not related directly to surface activity.