Membrane-bound form of fractalkine induces IFN-gamma production by NK cells.
Natural killer (NK) cells participate in both innate and adaptive immunity, in part by their prompt secretion of cytokines including IFN-gamma, a pro-inflammatory cytokine with an important role in Th1 polarization. To assess the involvement of fractalkine in inflammatory processes, we examined the effect of fractalkine on IFN-gamma production by NK cells. Although soluble chemokines, including MCP-1 and RANTES as well as fractalkine, had a negligible effect on IFN-gamma production, immobilized fractalkine markedly induced IFN-gamma production by NK cells in a dose-dependent manner. Pretreatment of NK cells with the phosphatidylinositol 3-kinase (PI 3-K) inhibitor, wortmannin, completely inhibited the production of IFN-gamma induced by fractalkine, and pretreatment with the protein tyrosine kinase inhibitor, herbimycin A, partially suppressed the response, suggesting that augmentation of IFN-gamma production in response to fractalkine treatment of NK cells involves signaling through PI 3-K and protein tyrosine kinases. Furthermore, co-culture of NK cells with fractalkine-transfected 293E cells markedly enhanced IFN-gamma production by NK cells compared with co-culture with control 293E cells. These findings may indicate a paracrine feedback loop system in which endothelial cells may be activated to produce more fractalkine, and also suggest a role for fractalkine expressed on endothelial cells in Th1 polarization through the stimulation of IFN-gamma production by NK cells.
Yoneda
Osamu
O
Department of Internal Medicine, Osaka Dental University, Osaka, Japan.
Imai
Toshio
T
Nishimura
Miyuki
M
Miyaji
Michihiko
M
Mimori
Tsuneyo
T
Okazaki
Toshiro
T
Domae
Naochika
N
Fujimoto
Hiroko
H
Minami
Yasuhiro
Y
Kono
Takeshi
T
Bloom
Eda T
ET
Umehara
Hisanori
H
D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D018920:Coculture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D014162:Transfection
C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D007371:Interferon-gamma