Re-expression of pulmonary surfactant proteins following tracheal obstruction in fetal sheep

Increased fetal lung expansion, induced by tracheal obstruction (TO), is a potent stimulus for fetal lung growth, but rapidly reduces surfactant prote in (SP) mRNA levels. Our aim was to determine the time course for the reexp ression of the surfactant proteins in fetal lung tissue following the relea se of a TO and to relate these to the changes in lung liquid volume. Fetal sheep were exposed to either: (1) no treatment (controls); (2) 4 days of TO ; (3) 4 days of TO, followed by release of the obstruction for 24 h; (4) 4 days of TO followed by release of the obstruction for 3 days. Four days of TO increased lung liquid volumes from 26.8 +/- 1.9 to 72.0 +/- 5.6 ml kg(-1 ) and reduced SP-A, SP-B and SP-C mRNA levels to 38.5 +/- 10.7, 56.8 +/- 10 .3 and 18.3 +/- 5.3 % of control values, respectively. One day after TO rel ease, lung liquid volumes were reduced to 17.4 +/- 5.3 ml kg(-1) (control 1 28 days, 31.0 +/- 3.8 ml kg(-1)) and SP-A and SP-B mRNA levels were not dif ferent from control levels. In contrast, SP-C mRNA levels only increased to 45.4 +/- 17.3 % of control. Three days after TO release, lung liquid volum es increased to 48.0 +/- 8.5 ml kg(-1) and SP-A and SP-B mRNA levels were r educed to 48.8 +/- 10.2 % and 71.5 +/- 19.8 % of control, respectively; SP- C mRNA levels remained at 35.3 +/- 12.3 % of control. Following the release of a TO, SP-A, SP-B and SP-C mRNA levels were closely and inversely relate d to the volume of lung liquid. Based on these relationships, the lung liqu id volumes that equate to 100 % expression were considerably less than cont rol lung volumes (< 10 vs. 30-40 ml kg(-1)) in fetuses of this age. Thus, t he changes in fetal lung SP-A, SP-B and SP-C mRNA levels following the rele ase of a TO are variable, differ between the proteins and are closely relat ed to the changes in lung liquid volumes. We conclude that the re-expressio n of surfactant proteins following TO is variable and that the change in lu ng liquid volume is potentially a good indicator for surfactant protein re- expression.