Enhanced neutrophil motility by granulocyte colony-stimulating factor: the role of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase.
The effect of granulocyte colony-stimulating factor (G-CSF) on human neutrophil motility was studied using videomicroscopy. Stimulation of neutrophils with G-CSF resulted in enhanced motility with morphological change and increased adherence. Enhanced neutrophil motility was detected within 3-5 min after G-CSF stimulation, reached a maximum at 10 min, and was sustained for approximately 35 min. The maximum migration rate was 84.4 +/- 2.9 microm/5 min. A study using the Boyden chamber method revealed that G-CSF-stimulated neutrophils exhibited random migration but not chemotaxis. Enhanced neutrophil motility and morphological change were inhibited by MEK [mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase] inhibitors (PD98059 and U0126), and a phosphatidylinositol 3-kinase (PI3K) inhibitor (wortmannin), but not by a p38 MAPK inhibitor (SB203580). These findings are consistent with the fact that G-CSF selectively activates MEK/ERK and PI3K, but not p38, in neutrophils. MEK/ERK activation was associated with G-CSF-induced redistribution of F-actin and phosphorylated myosin light chain. Enhanced neutrophil motility was observed even in the presence of neutralizing anti-CD18 antibody, which prevented cell adherence. These findings indicate that G-CSF induces human neutrophil migration via activation of MEK/ERK and PI3K.
Nakamae-Akahori
Mika
M
Department of Physiology, Osaka City University Graduate School of Medicine, Abenoku, Osaka, Japan.
Kato
Takayuki
T
Masuda
Sayuri
S
Sakamoto
Erina
E
Kutsuna
Haruo
H
Hato
Fumihiko
F
Nishizawa
Yoshiki
Y
Hino
Masayuki
M
Kitagawa
Seiichi
S
D000328:Adult; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D018715:Microscopy, Video; D018994:Myosin Light Chains / Q000378:metabolism; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology*; D010766:Phosphorylation; D015398:Signal Transduction / Q000276:immunology
D018994:Myosin Light Chains; D016179:Granulocyte Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases