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 incorporat ion into total phosphatidylcholine and type II cell-specific disaturat ed phosphatidylcholine (DPPC) in human fetal lung in culture. SP-A mRN A 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 phosp hatidylcholine and DPPC were both increased in human fetal lung explan ts incubated in increased O-2 concentrations compared with tissues inc ubated in 20% O-2. Tissue levels of adenosine 3',5'-cyclic monophospha te (cAMP)-dependent protein kinase (PKA) activity were not affected by O-2 concentration, implying that the changes observed in SP mRNA leve ls and [H-3]choline incorporation may not be mediated through alterati ons in PKA enzyme activity. These findings demonstrate that O-2 regula tes SP mRNA expression and phospholipid production in human fetal lung in vitro. We speculate that surfactant composition and possibly funct ion may be regulated by O-2 in human lung.