Am. J. Respir. Crit. Care Med.,
Volume 159, Number 2, February 1999, 613-618
Dioleylphosphatidylglycerol Inhibits the Expression
of Type II Phospholipase A2 in Macrophages
ARNAUD
BERGER,
NATHALIE
HAVET,
DANIEL
VIAL,
LAURENCE
ARBIBE,
CLAUDE
DUMAREY,
MALCOM L.
WATSON,
and
LHOUSSEINE
TOUQUI
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-INSERM No. 485, Paris, France; and Department of
Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom
We have recently shown that modified natural pulmonary surfactant Curosurf inhibits the synthesis of
type II phospholipase A2 (sPLA2-II) by cultured guinea-pig alveolar macrophages (AM). The goal of
the present study was to identify the surfactant components and the mechanisms involved in this process. We show that protein-free artificial surfactant (AS) mimicked the inhibitory effect of Curosurf, suggesting that phospholipid components of surfactant play a role in the inhibition of sPLA2-II expression. Among surfactant phospholipids, dioleylphosphatidylglycerol (DOPG) was the most effective in inhibiting the synthesis of sPLA2-II. By contrast, the concentrations of platelet-activating factor
(PAF)-acetylhydrolase and lysophospholipase activities remained unchanged, indicating that inhibition of sPLA2-II synthesis was caused by a specific effect of surfactant. The effect of DOPG on sPLA2-II
synthesis was concentration-dependent and was accompanied by a rapid and time-dependent uptake
of DOPG by AM whereas dipalmitoylphosphatidylcholine (DPPC) was only marginally taken up. Curosurf, AS, and DOPG inhibited tumor necrosis factor-alpha (TNF-
) secretion, a key step in the induction of sPLA2-II synthesis by AM, in contrast to DPPC which had only a marginal effect. We conclude
that phospholipid components, especially DOPG, play a major role in the inhibition of sPLA2-II synthesis by surfactant and that this effect can be explained, at least in part, by an impairment of TNF- secretion.
