EPSTEIN-BARR-VIRUS MODULATES 5-LIPOXYGENASE PRODUCT SYNTHESIS IN HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

The effect of short-term coincubations of Epstein-Barr virus (EBV) wit h mononuclear cells on the synthesis of leukotrienes (LT) by monocytes was investigated. Although treatment of mononuclear cells with EBV al one had no significant effect on LT synthesis by monocytes, the preinc ubation of mononuclear cells with EBV before the further stimulation o f the cells with either the ionophore A23187, the chemoattractant form yl-Met-Leu-Phe, or the phagocytic particles zymosan strikingly enhance d the formation of both LTB(4) and LTC, above the levels of synthesis observed with the stimuli alone. Such priming effect of EBV on LT synt hesis was maximal after 15 minutes of preincubation of mononuclear cel ls with EBV and slowly declined at longer preincubation times; the pri ming effect of EBV was observed both in Hank's Balanced Salt Solution and plasma, The effect of EBV was abolished by prior treatment of vira l particles by heat or by antibody raised against the glycoprotein gp3 50 of the viral envelope, but not by UV irradiation of the viral parti cles, Exposure of mononuclear cells to EBV was shown to strongly enhan ce 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 inhibita ble by arachidonyl trifluoromethyl ketone, an inhibitor of the 80-kD c ytosolic phospholipase A(2). Furthermore, EBV was shown to rapidly inc rease (maximum effect within 15 minutes) the levels of phosphorylated form of the cytosolic phospholipase A(2) (as assessed by sodium dodecy l sulfate-polyacrylamide gel electrophoresis and immunoblot analysis), a process related to the activation of this enzyme, These data show t hat the interaction of EBV with monocytes upregulates the formation of important lipid mediators of inflammation. (C) 1997 by The American S ociety of Hematology.