OXYGEN MODULATES SURFACTANT PROTEIN MESSENGER-RNA EXPRESSION AND PHOSPHOLIPID PRODUCTION IN HUMAN FETAL LUNG IN-VITRO

We studied the effect of 20-95% O-2 on mRNA levels for the surfactant-associated proteins (SP)-A, SP-B, and SP-C and [H-3]choline incorporation into total phosphatidylcholine and type II cell-specific disaturated phosphatidylcholine (DPPC) in human fetal lung in culture. SP-A mRNA levels were increased by 25 and 39% in lung explants incubated in 70 and 95% O-2, respectively, compared with levels in tissues incubated in 20% O-2. SP-B mRNA levels were unaffected by O-2, whereas SP-C mRNA levels were increased by 85, 102, and 115% in atmospheres of 35, 50, and 70% O-2, respectively. [H-3]choline incorporation into total phosphatidylcholine and DPPC were both increased in human fetal lung explants incubated in increased O-2 concentrations compared with tissues incubated in 20% O-2. Tissue levels of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) activity were not affected by O-2 concentration, implying that the changes observed in SP mRNA levels and [H-3]choline incorporation may not be mediated through alterations in PKA enzyme activity. These findings demonstrate that O-2 regulates SP mRNA expression and phospholipid production in human fetal lung in vitro. We speculate that surfactant composition and possibly function may be regulated by O-2 in human lung.