Stabilization of lung surfactant particles against conversion by a
cycling interface.
Hall, S. B., R. W. Hyde, and M. C. Kahn.
Department of Medicine, Oregon Health Sciences University,
Portland, Oregon and Departments of Medicine and Environmental
Medicine, University of Rochester, Rochester, New York
APStracts 3:0207L, 1996.
The large active particles of pulmonary surfactant are depleted in
patients with the Acute Respiratory Distress Syndrome and in animal
models of this disorder. We studied in vitro conversion of large to
small particles, separated by differential sedimentation, to
determine how factors lavaged from rabbits injured by intravenous
oleic acid would affect conversion. In half-filled test tubes rotated
end-over-end, samples from 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 by Gross and
Schultz to block conversion (9), stabilized surfactant particles by
limiting access to the cycling interface. Hemoglobin, neutrophil
elastase, and [alpha]1-antiproteinase ([alpha]1-PI) oxidized to
eliminate its antiproteinase activity all stabilized large particles
against conversion. Hemoglobin was most effective, increasing
recovery from 18 +/- 5% for controls to 86 +/- 5% with 0.4 mg/ml
hemoglobin. Native [alpha]1-PI had no effect on conversion. Our
results suggest 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 sedimentation requires no proteinase susceptible to
inhibition by [alpha]1-PI. They provide an alternate hypothesis
related to interfacial effects rather than proteinase inhibition for
the previously reported effect of [alpha]1-PI on conversion of
particles separated according to density.
Received 5 September 1995; accepted in final form 7 October 1996.
APS Manuscript Number L268-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996