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

Abstract

Increased fetal lung expansion, induced by tracheal obstruction (TO), is a potent stimulus for fetal lung growth, but rapidly reduces surfactant protein (SP) mRNA levels. Our aim was to determine the time course for the re-expression of the surfactant proteins in fetal lung tissue following the release 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 release, lung liquid volumes were reduced to 17.4 +/- 5.3 ml kg(-1) (control 128 days, 31.0 +/- 3.8 ml kg(-1)) and SP-A and SP-B mRNA levels were not different 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 volumes increased to 48.0 +/- 8.5 ml kg(-1) and SP-A and SP-B mRNA levels were reduced 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 related to the volume of lung liquid. Based on these relationships, the lung liquid volumes that equate to 100 % expression were considerably less than control lung volumes (< 10 vs. 30-40 ml kg(-1)) in fetuses of this age. Thus, the changes in fetal lung SP-A, SP-B and SP-C mRNA levels following the release of a TO are variable, differ between the proteins and are closely related to the changes in lung liquid volumes. We conclude that the re-expression of surfactant proteins following TO is variable and that the change in lung liquid volume is potentially a good indicator for surfactant protein re-expression. Experimental Physiology (2001) 86.1, 55-63.