Enhancement of biophysical activity of lung surfactant extracts and phospholipid-apoprotein mixtures by surfactant protein A

A. R. Venkitaraman, S. B. Hall, J. A. Whitsett, R. H. Notter

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

The effects of surfactant protein (SP)-A on the dynamic surface tension lowering and resistance to inhibition of dispersions of calf lung surfactant extract (CLSE) and mixtures of synthetic phospholipids combined with SP-B, C hydrophobic apoproteins were studied at 37°C and rapid cycling rate (20 cyles/min). Addition of SP-A to CLSE, which already contains SP-B and -C, gave a slight improvement in the time course of surface tension lowering on an oscillating bubble apparatus in the absence of inhibitory protein molecules such as albumin or hemoglobin. However, when these proteins were present at concentrations of 10-50 mg/ml, SP-A substantially improved the resistance of CLSE to their inhibitory effects. The beneficial effect of SP-A required the presence of Ca2+ ions, and disappeared when EDTA was substituted for this divalent cation in the subphase. The effect was also retained when SP-A was heated to 50°C prior to addition to CLSE, but was abolished by heating SP-A to 99°C. Additional studies showed that similar improvements in resistance to inhibition were found when SP-A was added to synthetic mixtures of dipalmitoyl phosphatidylcholine (DPPC):egg phosphatidylgylcerol (PG) (80:20 by weight) reconstituted with 1% SP-B or SP-B and -C, but not to phospholipid mixtures containing only SP-C. The requirements for SP-B and calcium for the beneficial effects of SP-A on surface activity suggest that the formation of ordered, larger phospholipid-apoprotein aggregates may be involved in the process. The finding that SP-A enhances the ability of CLSE and other surfactant mixtures containing SP-B to resist inhibition is an advantage that will need to be weighed against other factors such as increased antigenicity and heat sensitivity in the therapeutic applications in surfactant replacement therapy.

Original languageEnglish (US)
Pages (from-to)185-193
Number of pages9
JournalChemistry and Physics of Lipids
Volume56
Issue number2-3
DOIs
StatePublished - Dec 1990

Keywords

  • adult respiratory distress syndrome
  • dynamic surface tension lowering
  • pulmonary surfactants
  • surfactant apoproteins
  • surfactant inhibition

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Cell Biology

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