Epstein-Barr virus induces GM-CSF synthesis by monocytes: effect on EBV-induced IL-1 and IL-1 receptor antagonist production in neutrophils.
Neutrophils play an important role in the control of viral infections by releasing a variety of potent agents. We previously demonstrated that Epstein-Barr virus (EBV) binds to human neutrophils and stimulates cytokine synthesis including interleukin-1 (IL-1) and IL-1 receptor antagonist (IL-1Ra). Since neutrophil functions are known to be modulated by the priming effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), we therefore investigated the cellular source of GM-CSF synthesis following treatment of leukocytes with EBV and the effect of GM-CSF on the production of IL-1, IL-1Ra, and superoxide by EBV-treated neutrophils. In enriched-cell populations, only monocytes were found to produce GM-CSF in response to EBV, which was maximal after 12 h of incubation. The results obtained with UV-irradiated particles or EBV neutralized with monoclonal antibody 72A1 suggest that contact between the cell and the gp350 of the viral envelope is sufficient to induce the release of GM-CSF. On the other hand, GM-CSF differentially upregulated EBV-induced IL-1 and IL-1Ra production by neutrophils. Pretreatment of neutrophils with GM-CSF prior to EBV activation synergistically enhanced the production of IL-1 alpha and IL-1 beta, but only marginally affected IL-1Ra synthesis. In addition, GM-CSF was also found to synergistically enhance the superoxide production by neutrophils in response to EBV. Molecular analysis showed that GM-CSF did not alter the IL-1 beta and IL-1Ra mRNA synthesis induced by EBV, suggesting that GM-CSF could act at a posttranslational level. Local production of GM-CSF by monocytes in tissues invaded by EBV could serve to potentiate the host defense mechanisms directed toward the destruction of the infectious virus.
Roberge
C J
CJ
Laboratory of Viral Immunology, CHUL, Laval University, Quebec, Canada.
Larochelle
B
B
Rola-Pleszczynski
M
M
Gosselin
J
J
D000818:Animals; D015152:Blotting, Northern; D002144:Callithrix; D002461:Cell Line, Transformed; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis*; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D013481:Superoxides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor