Effects of platelet-activating factor on peripheral blood monocytes: induction and priming for TNF secretion.
Inflammatory-type responses are complex events involving several cellular interactions and several cytokines. Both the monocytes/macrophages and platelet-activating factor (PAF) play an important and central role in inflammatory responses. Accordingly, we investigated the effects of PAF on function and priming of human peripheral blood monocytes (PBM). Several observations were made that demonstrated that PBM respond to PAF stimulation. The addition of PAF to freshly isolated PBM triggered the release of tumor necrosis factor (TNF) in the supernatant in the absence of induction of macrophage-mediated cytotoxicity, unlike interferon-gamma (IFN-gamma) or lipopolysaccharide (LPS). Secretion of TNF was detected shortly after addition of PAF and was dependent on the PAF concentration used. By 4-6 h, the level of TNF, as detected by radioimmunoassay, reached a plateau and remained the same for 24 h. While biologically active and cytotoxic TNF was detected early after addition of PAF, the cytotoxic activity declined thereafter though the antigenic activity remained constant. Supernatants derived from PAF-treated PBM contained an inhibitor of TNF biological activity. We then examined whether PBM can be primed with PAF and respond to a secondary challenge. PBM primed with PAF respond by secreting TNF to both phorbol myristate acetate and concanavalin A but respond poorly to PAF, LPS, or IFN-gamma. These results suggest that following priming, PBM remain refractory to specific secondary stimuli but can still respond to non-specific stimuli. Overall, the present findings demonstrate that PAF can directly interact with PBM and regulate their functional activity. We suggest that PAF may mediate part of its biological activity via the macrophage and further, monocyte secretion of PAF can in turn regulate monocyte function. Further, cytokine secretion by PAF-activated PBM may contribute to the inflammatory process.
Bonavida
B
B
Department of Microbiology and Immunology, UCLA School of Medicine, University of California 90024.
Mencia-Huerta
J M
JM
Braquet
P
P
D002118:Calcium / Q000378:metabolism; D003208:Concanavalin A / Q000008:administration & dosage; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000008:administration & dosage; D008070:Lipopolysaccharides / Q000008:administration & dosage; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010972:Platelet Activating Factor / Q000008:administration & dosage* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium