Activation of human neutrophils by granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha: role of phosphatidylinositol 3-kinase.
Stimulation of human neutrophils with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), or tumor necrosis factor alpha (TNF) resulted in phosphorylation of Akt, the potency being GM-CSF > G-CSF = TNF, which was inhibited by wortmannin. The findings indicated that phosphatidylinositol 3-kinase (PI3K) is activated by these cytokines. The possible participation of PI3K in activation of neutrophil functions induced by these cytokines was explored with PI3K inhibitors (wortmannin and LY294002). Superoxide release and adherence induced by GM-CSF or TNF were inhibited by PI3K inhibitors. Actin reorganization and morphological changes induced by G-CSF or GM-CSF were also inhibited by wortmannin, whereas these responses induced by TNF were unaffected by wortmannin. These findings suggested that PI3K is differentially involved in cytokine-mediated activation of neutrophil functions depending on the cytokines used. The results also showed that activation of extracellular signal-regulated kinase, but not p38 mitogen-activated protein kinase, induced by these cytokines is partly mediated by PI3K activation.
Kamata
Noriko
N
Department of Physiology, Osaka City University Medical School, Osaka, Japan.
Kutsuna
Haruo
H
Hato
Fumihiko
F
Kato
Takayuki
T
Oshitani
Nobuhide
N
Arakawa
Tetsuo
T
Kitagawa
Seiichi
S
D000730:Androstadienes / Q000494:pharmacology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D016207:Cytokines; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one