Inhibition of pulmonary surfactant by oleic acid: Mechanisms and characteristics

S. B. Hall, R. Z. Lu, A. R. Venkitaraman, R. W. Hyde, R. H. Notter

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

The inhibitory effects of oleic acid (OA) on the surface activity of pulmonary surfactant were characterized by use of the oscillating bubble surfactometer, the Wilhelmy balance, and excised rat lungs. Oscillating bubble studies showed that OA prevented lavaged calf surfactant [0.5 mM phospholipid (PL)] from lowering surface tension below 15 mN/m at or above a molar ratio of OA/PL = 0.5. In contrast to inhibition of surfactant by plasma proteins, increasing the surfactant concentration did not eliminate inhibition by oleic acid, which occurred at OA/PL >0.67 on the oscillating bubble even at surfactant concentrations of 1.5 and 12 mM PL. Studies of surfactant adsorption showed that preformed films of OA had little effect on the adsorption of pulmonary surfactant. Wilhelmy balance studies showed that OA did interfere with the ability of spread films of surfactant to reach low surface tensions during dynamic compression. Further balance experiments with binary films of OA and dipalmitoyl phosphatidylcholine showed that these compounds were miscible in surface films. Together these findings suggested that OA inhibited pulmonary surfactant activity by disrupting the rigid interfacial film responsible for the generation of very low surface tension during dynamic compression. Mechanical studies in excised rat lungs showed that instillation of OA gave altered deflation pressure-volume characteristics with decreased quasi-static compliance, indicating disruption of pulmonary surfactant function in situ. This alteration of mechanics occurred without major changes in the composition of lavaged PLs or in the tissue compliance of the lungs defined by mechanical measurements during inflation-deflation with saline. These results indicate that OA can inhibit pulmonary surfactant activity by mechanisms and with concentration dependence substantially different from those previously demonstrated for plasma proteins. In lung injuries in which multiple inhibitors are present, additive interactions among proteins and lipids may lead to more severe inhibition of surfactant function.

Original languageEnglish (US)
Pages (from-to)1708-1716
Number of pages9
JournalJournal of Applied Physiology
Volume72
Issue number5
StatePublished - Jan 1 1992

Keywords

  • adult respiratory distress syndrome
  • free fatty acid
  • lung injury
  • surfactant inhibition

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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    Hall, S. B., Lu, R. Z., Venkitaraman, A. R., Hyde, R. W., & Notter, R. H. (1992). Inhibition of pulmonary surfactant by oleic acid: Mechanisms and characteristics. Journal of Applied Physiology, 72(5), 1708-1716.