Abstract
We provide evidence that platelet factor 4 (PF4), but not the related chemokine neutrophil-activating polypeptide-2, induced highly purified human natural killer (NK) cells to produce interleukin (IL)-8 in a time- and dosage-dependent manner. This ability was retained even while PF4 was bound to heparin. PF4 increased the steady state level of IL-8 mRNA, likely implying a transcriptional effect of PF4. Stimulation of NK cells through the Fc receptor for immunoglobulin G-IIIA was found to synergistically increase the effect of PF4 on IL-8 production but did not affect IL-2-related activities such as cytotoxic activity and proliferation. Pertussis toxin did not block the PF4-derived IL-8 production in NK cells, but this response was sensitive to wortmannin, implicating a role of phosphatidylinositol 3-kinase in the intracellular signaling pathway triggered by PF4. Our results characterize a new capacity for PF4 and provide further evidence for the pivotal role of NK cells in the environment of inflammation.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Antibodies, Monoclonal / pharmacology
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Cells, Cultured / drug effects
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Dose-Response Relationship, Drug
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Heparin / chemistry
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Humans
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Immunoglobulin Fc Fragments / immunology
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Immunoglobulin Fc Fragments / physiology
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Interleukin-8 / biosynthesis*
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Interleukin-8 / genetics
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Interleukin-8 / metabolism
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Killer Cells, Natural / drug effects*
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Killer Cells, Natural / metabolism
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Peptides / pharmacology
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Pertussis Toxin
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Phosphatidylinositol 3-Kinases / physiology
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Platelet Factor 4 / chemistry
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Platelet Factor 4 / pharmacology*
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RNA, Messenger / biosynthesis
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Recombinant Fusion Proteins / pharmacology
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Transcription, Genetic / drug effects
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Virulence Factors, Bordetella / pharmacology
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beta-Thromboglobulin
Substances
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Antibodies, Monoclonal
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Immunoglobulin Fc Fragments
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Interleukin-8
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PPBP protein, human
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Peptides
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RNA, Messenger
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Recombinant Fusion Proteins
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Virulence Factors, Bordetella
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beta-Thromboglobulin
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Platelet Factor 4
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Heparin
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Pertussis Toxin
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Phosphatidylinositol 3-Kinases