Regulation of platelet-activating factor synthesis in human monocytes by dipalmitoyl phosphatidylcholine.

AJ Tonks, A Tonks, Roger H.K. Morris, Kenneth P. Jones, Simon K. Jackson

Research output: Contribution to journalArticlepeer-review

Abstract

Platelet-activating factor (PAF) has a major role in inflammatory responses within the lung. This study investigates the effect of pulmonary surfactant on the synthesis of PAF in human monocytic cells. The pulmonary surfactant preparation Curosurf significantly inhibited lipopolysaccharide (LPS)-stimulated PAF biosynthesis (P<0.01) in a human monocytic cell line, Mono mac-6 (MM6), as determined by (3)H PAF scintillation-proximity assay. The inhibitory properties of surfactant were determined to be associated, at least in part, with the 1,2-dipalmitoyl phosphatidylcholine (DPPC) component of surfactant. DPPC alone also inhibited LPS-stimulated PAF biosynthesis in human peripheral blood monocytes. DPPC treatment did not affect LPS-stimulated phospholipase A(2) activity in MM6 cell lysates. However, DPPC significantly inhibited LPS-stimulated coenzyme A (CoA)-independent transacylase and acetyl CoA:lyso-PAF acetyltransferase activity. DPPC treatment of MM6 cells decreased plasma membrane fluidity as demonstrated by electron paramagnetic resonance spectroscopy coupled with spin labeling. Taken together, these findings indicate that pulmonary surfactant, particularly the DPPC component, can inhibit LPS-stimulated PAF production via perturbation of the cell membrane, which inhibits the activity of specific membrane-associated enzymes involved in PAF biosynthesis.
Original languageEnglish
Pages (from-to)95-101
Number of pages0
JournalJ Leukoc Biol
Volume74
Issue number1
DOIs
Publication statusPublished - Jul 2003

Keywords

  • 1
  • 2-Dipalmitoylphosphatidylcholine
  • Acetyltransferases
  • Acyltransferases
  • Cell Line
  • Humans
  • Lipopolysaccharides
  • Membrane Fluidity
  • Monocytes
  • Platelet Activating Factor
  • Pulmonary Surfactants
  • Respiratory Distress Syndrome

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