Granulocyte-macrophage colony-stimulating factor enhances EBV-induced synthesis of chemotactic factors in human neutrophils.
We have recently demonstrated that EBV binds to human neutrophils and stimulates a wide range of activities, including homeotypic aggregation, total RNA synthesis, and expression of the chemokines IL-8 and macrophage inflammatory protein-1alpha (MIP-1alpha). Neutrophil function is also known to be modulated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF). We have therefore investigated the modulation of EBV-induced activation of human neutrophils by GM-CSF. Treatment of neutrophils with GM-CSF before EBV activation enhanced the production of both MIP-1alpha and IL-8. The IL-8 produced under these conditions was biologically active as determined in the calcium mobilization assay. GM-CSF was also found to increase the ability of EBV to prime neutrophils for increased leukotriene B4 (LTB4) synthesis. Prior treatment of GM-CSF with neutralizing Abs inhibited these effects. GM-CSF also increased the specific binding of FITC-EBV to the neutrophil surface, as evaluated by fluorocytometry. Local production of GM-CSF in tissues invaded by EBV could therefore serve to potentiate a host defense mechanism directed toward the destruction of the infectious virus via increased production of chemotactic factors. Since both IL-8 and MIP-1alpha are reported to be chemoattractants in vitro for T cells and T and B cells, respectively, the ability of EBV to induce their production by neutrophils may enhance its ability to infect B and T lymphocytes via increased recruitment to sites of infection.
Roberge
C J
CJ
Viral Immunology Laboratory, Centre de Recherche du Centre Hospitalier de l'Université Laval, Québec, Canada.
McColl
S R
SR
Larochelle
B
B
Gosselin
J
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002630:Chemotactic Factors / Q000096:biosynthesis*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics; D018375:Neutrophil Activation / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D012333:RNA, Messenger / Q000378:metabolism
D000276:Adjuvants, Immunologic; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002630:Chemotactic Factors; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D007975:Leukotriene B4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002118:Calcium