Epstein-Barr virus primes human polymorphonuclear leucocytes for the biosynthesis of leukotriene B4.
In the present study, we have investigated the effect of the short-term incubation of polymorphonuclear leucocytes (PMN) with infectious Epstein-Barr virus (EBV) on leukotriene B(4) (LTB(4)) biosynthesis. Pre-exposure of PMN to EBV led to an increased production of LTB(4) upon stimulation with either the ionophore A23187, the chemotactic peptide fMLP, or phagocytic particles (zymosan). Experiments performed with viral particles pretreated with a neutralizing antibody raised against the gp350 of the viral envelope revealed that a specific interaction between the PMN surface and the viral glycoprotein gp350 is required for the priming effect of EBV. Preincubation of PMN with EBV resulted in an increased release of arachidonic acid upon stimulation with a second agonist. Moreover, LTB(4) biosynthesis in EBV/A23187-treated PMN was greatly diminished in the presence of an inhibitor of the cytosolic phospholipase A2 (cPLA(2)), suggesting that cPLA(2) plays a critical role in the priming effect of EBV. Accordingly, EBV by itself promoted Ser-505 phosphorylation of cPLA(2) and strongly enhanced fMLP-induced phosphorylation of p38 MAP kinase, an enzyme known to phosphorylate cPLA(2) in human PMN. Furthermore, fMLP-induced translocation of cPLA(2) was strongly enhanced when PMN were previously exposed to EBV. These data indicate that binding of EBV to human PMN results in the activation of intracellular events involved in the release of pro-inflammatory lipid mediators.
Gosselin
J
J
Laboratory of Viral Immunology, Centre de recherche en Rhumatologie et Immunologie, Centre de recherche du CHUL (CHUQ), and Université Laval, Québec, Canada. Jean.Gosselin@crchul.ulaval.ca
Savard
M
M
Tardif
M
M
Flamand
L
L
Borgeat
P
P
D016718:Arachidonic Acid / Q000096:biosynthesis; D000001:Calcimycin / Q000494:pharmacology; D020013:Calcium Signaling; D004789:Enzyme Activation; D020031:Epstein-Barr Virus Infections / Q000209:etiology / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010766:Phosphorylation; D014779:Virus Replication; D015054:Zymosan / Q000494:pharmacology
D007476:Ionophores; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D020928:Mitogen-Activated Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2