Inhibition of lung calcium-independent phospholipase A2 by surfactant protein A

Am J Physiol. 1994 Sep;267(3 Pt 1):L335-41. doi: 10.1152/ajplung.1994.267.3.L335.


The effect of lung surfactant protein A (SP-A) on lung phospholipase A2 (PLA2) activity was investigated. SP-A was purified from bovine surfactant obtained by lung lavage. PLA2 was assayed using radiolabeled 1,2-dipalmitoyl phosphatidylcholine (DPPC) in surfactant-like unilamellar liposomes with Ca(2+)-free acidic (pH 4) or 10 mM Ca2+, alkaline (pH 8.5) buffer. SP-A significantly inhibited Ca(2+)-independent acidic PLA2 of rat lung homogenate or isolated lamellar bodies but had no effect on the Ca(2+)-dependent alkaline enzyme. Lamellar body PLA2 was inhibited by 50% with 0.25 micrograms SP-A/microgram lamellar body protein. Similar inhibition by SP-A was observed when 1-palmitoyl,2-oleoyl PC (POPC) was the substrate. Binding assay showed binding of 125I-labeled SP-A to DPPC but not to POPC, indicating that removal of substrate was not the mechanism for inhibition of the enzyme by SP-A. Chemical reduction or alkylation of SP-A abolished its inhibitory effect on PLA2 activity. Inactivation of endogenous SP-A in isolated lamellar bodies or surfactant increased Ca(2+)-independent PLA2 activity in these fractions. The presence of SP-A in liposomes stimulated the uptake of DPPC by isolated granular pneumocytes in primary culture but significantly inhibited its degradation. These results indicate that the Ca(2+)-independent acidic PLA2 has a role in the metabolism of internalized surfactant phospholipid and that SP-A can modulate the activity of this enzyme.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1,2-Dipalmitoylphosphatidylcholine / metabolism
  • Animals
  • Calcium / physiology*
  • Cattle
  • Cells, Cultured
  • Glycerophosphates / pharmacology
  • Iodoacetamide / pharmacology
  • Lung / cytology
  • Lung / drug effects
  • Lung / metabolism*
  • Male
  • Mercaptoethanol / pharmacology
  • Phospholipases A / antagonists & inhibitors
  • Phospholipases A / metabolism*
  • Phospholipases A2
  • Proteolipids / pharmacology*
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactant-Associated Proteins
  • Pulmonary Surfactants / pharmacology*
  • Rats
  • Rats, Sprague-Dawley


  • Glycerophosphates
  • Proteolipids
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactant-Associated Proteins
  • Pulmonary Surfactants
  • 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol
  • 1,2-Dipalmitoylphosphatidylcholine
  • Mercaptoethanol
  • Phospholipases A
  • Phospholipases A2
  • Calcium
  • Iodoacetamide