STABILIZATION OF LUNG SURFACTANT PARTICLES AGAINST CONVERSION BY A CYCLING INTERFACE

The large active particles of pulmonary surfactant are depleted in pat ients with acute respiratory distress syndrome and in animal models of this disorder. We studied in vitro conversion of large to small parti cles, separated by differential sedimentation, to determine how factor s lavaged from rabbits injured by intravenous oleic acid would affect conversion. In half-filled test tubes rotated end over end, samples fr om injured animals increased the recovery of large particles from 40 /- 6% of uncycled samples for controls to 62 +/- 21%. We hypothesized that proteins in the injured samples, and perhaps also the proteinase inhibitors used previously to block conversion (N. J. Gross and R. M. Schultz. Biochim. Biophys. Acta 1044: 222-230, 1990), stabilized surfa ctant particles by limiting access to the cycling interface. Hemoglobi n, neutrophil elastase, and alpha(1)-antiproteinase (alpha(1)-PI) oxid ized to eliminate its antiproteinase activity all stabilized large par ticles against conversion. Hemoglobin was most effective, increasing r ecovery from 18 +/- 5% for controls to 86 +/- 5% with 0.4 mg/ml hemogl obin. Native alpha(1)-PI had no effect on conversion. Our results sugg est that acceleration of normal conversion is unlikely to explain the depletion of large particles in injured lungs. They also suggest that conversion of surfactant particles separated by differential sedimenta tion requires no proteinase susceptible to inhibition by alpha(1)-PI. They provide an alternate hypothesis related to interfacial effects ra ther than proteinase inhibition for the previously reported effect of alpha(1)-PI on conversion of particles separated according to density.