Oxygen modulates surfactant protein mRNA expression and phospholipid production in human fetal lung in vitro

Abstract

We studied the effect of 20-95% O2 on mRNA levels for the surfactant-associated proteins (SP)-A, SP-B, and SP-C and [3H]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% O2, respectively, compared with levels in tissues incubated in 20% O2. SP-B mRNA levels were unaffected by O2, whereas SP-C mRNA levels were increased by 85, 102, and 115% in atmospheres of 35, 50, and 70% O2, respectively. [3H]choline incorporation into total phosphatidylcholine and DPPC were both increased in human fetal lung explants incubated in increased O2 concentrations compared with tissues incubated in 20% O2. Tissue levels of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) activity were not affected by O2 concentration, implying that the changes observed in SP mRNA levels and [3H]choline incorporation may not be mediated through alterations in PKA enzyme activity. These findings demonstrate that O2 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 O2 in human lung.