Secretagogues for lung surfactant increase lung uptake of alveolar phospholipids

This study evaluated the effect of known secretagogues for lung surfactant on the uptake of phospholipid from the aveolar space. Synthetic liposomes containing tracer [choline-methyl-3H]dipalmitoyl phosphatidylcholine (DPPC) were instilled endotracheally in anesthetized rats. Lungs were then isolated and perfused under control conditions or with addition of terbutaline (0.1 mM), ATP (1 mM), or a phorbol ester, tradecanoyl phorbol acetate (TPA, 30 ng/ml). Uptake of liposomes was defined as lavage-resistant accumulation of radioactivity in the lung. Uptake at 2 h was 18.2 +/- 0.93% of instilled radioactivity per minute (mean +/- SE, n = 4) under control conditions and was increased by 56-82% in the presence of each of the agonists (P less than 0.05). At 5 min after addition of terbutaline, uptake was unchanged but secretion of phosphatidylcholine (PC) into the alveolar space was significantly stimulated. Internalized diphosphatidylcholine was degraded to aqueous soluble metabolites and also converted to PC containing an unsaturated fatty acid, and this metabolism was significantly stimulated in the presence of each of the secretagogues. These results indicate that known secretagogues for surfactant increase uptake and metabolism of phospholipid, suggesting linkage of these processes in a physiologically regulated surfactant cycle.

Oxygen-induced changes in pulmonary phospholipids in the rat

The composition and synthesis of alveolar and lung tissue phospholipids were investigated in normal and oxygen-poisoned rat lungs. Sixty-hour exposure to oxygen increased the total amount of phospholipids in the endobronchial extracts and lung tissue. Phosphatidyl glycerol was identified in both endobronchial extracts and lung tissue. The amount of unsaturated fatty acids in surfactant lecithin and phosphatidyl glycerol was slightly increased in oxygen-poisoned lungs whereas the composition of phospholipids in the endobronchial extracts was not affected by oxygen. After intraperitoneal administration of [32P]phosphate the specific activities of surfactant lecithin and phosphatidyl glycerol were clearly lower in oxygen-treated animals whereas the specific activities of lung tissue lecithin and phosphatidyl glycerol remained unaffected. The synthesis of lecithin from [14C]methionine through N-methyltransferase pathway was markedly depressed in lung slices but increased in liver tissue taken from oxygen-poisoned rats and incubated under oxygen indicating a difference between lung and liver methyltransferase enzymes. In conclusion, the present work suggests impaired synthesis and removal of alveolar phospholipids in oxygen-poisoned rats.