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Epstein-Barr virus modulates 5-lipoxygenase product synthesis in human
peripheral blood mononuclear cells
J Gosselin and P Borgeat
Laboratory of Viral Immunology, Centre de recherche en Rhumatologie et
Immunologie, Universite Laval, Quebec, Canada.
The effect of short-term coincubations of Epstein-Barr virus (EBV) with
mononuclear cells on the synthesis of leukotrienes (LT) by monocytes was
investigated. Although treatment of mononuclear cells with EBV alone had no
significant effect on LT synthesis by monocytes, the preincubation of
mononuclear cells with EBV before the further stimulation of the cells with
either the ionophore A23187, the chemoattractant formyl-Met-Leu-Phe, or the
phagocytic particles zymosan strikingly enhanced the formation of both LTB4
and LTC4 above the levels of synthesis observed with the stimuli alone.
Such priming effect of EBV on LT synthesis was maximal after 15 minutes of
preincubation of mononuclear cells with EBV and slowly declined at longer
preincubation times; the priming effect of EBV was observed both in Hank's
Balanced Salt Solution and plasma. The effect of EBV was abolished by prior
treatment of viral particles by heat or by antibody raised against the
glycoprotein gp350 of the viral envelope, but not by UV irradiation of the
viral particles. Exposure of mononuclear cells to EBV was shown to strongly
enhance the activation of the 5-lipoxygenase and the release of arachidonic
acid induced upon cell stimulation with a second agonist. The release of
arachidonic acid by the EBV-treated mononuclear cells was inhibitable by
arachidonyl trifluoromethyl ketone, an inhibitor of the 80-kD cytosolic
phospholipase A2. Furthermore, EBV was shown to rapidly increase (maximum
effect within 15 minutes) the levels of phosphorylated form of the
cytosolic phospholipase A2 (as assessed by sodium dodecyl
sulfate-polyacrylamide gel electrophoresis and immunoblot analysis), a
process related to the activation of this enzyme. These data show that the
interaction of EBV with monocytes upregulates the formation of important
lipid mediators of inflammation.
Volume 89,
Issue 6,
pp. 2122-2130,
03/15/1997
Copyright © 1997 by The American Society of Hematology
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