Platelet factor 4 induces human natural killer cells to synthesize and release interleukin-8.
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.
Martí
Francesc
F
Laboratory of Cancer Immunology, Department of Cryobiology and Cell Therapy, Cancer Research Institute, Barcelona, Spain.
Bertran
Esther
E
Llucià
Montserrat
M
Villén
Esther
E
Peiró
Matilde
M
Garcia
Joan
J
Rueda
Fèlix
F
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000737:chemistry; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology / Q000502:physiology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010978:Platelet Factor 4 / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D001620:beta-Thromboglobulin
D000911:Antibodies, Monoclonal; D007141:Immunoglobulin Fc Fragments; D016209:Interleukin-8; C061615:PPBP protein, human; D010455:Peptides; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D010566:Virulence Factors, Bordetella; D001620:beta-Thromboglobulin; D010978:Platelet Factor 4; D006493:Heparin; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases