Enhanced neutrophil motility by granulocyte colony‐stimulating factor: the role of extracellular signal‐regulated kinase and phosphatidylinositol 3‐kinase
Enhanced neutrophil motility by granulocyte colony‐stimulating factor: the role of extracellular signal‐regulated kinase and phosphatidylinositol 3‐kinase
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DOI：
10.1111/j.1365-2567.2006.02448.x
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发表时间：
2006-11
期刊：
影响因子：
6.4
通讯作者：
Mika Nakamae-Akahori;Takayuki Kato;Sayuri Masuda;E. Sakamoto;H. Kutsuna;F. Hato;Y. Nishizawà;M. Hino;S. Kitagawa
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文献类型：
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作者：
Mika Nakamae-Akahori;Takayuki Kato;Sayuri Masuda;E. Sakamoto;H. Kutsuna;F. Hato;Y. Nishizawà;M. Hino;S. Kitagawa
使用视频显微镜研究了粒细胞集落刺激因子（G-CSF）对人中性粒细胞运动的影响。用G-CSF刺激中性粒细胞导致运动性增强、形态学改变和粘附性增加。在G-CSF刺激后3 - 5 min内检测到中性粒细胞运动增强，在10 min时达到最大值，并持续约35 min。最大迁移率为84.4 ± 2.9 μ m/5 min。使用Boyden小室法的研究显示，G-CSF刺激的中性粒细胞表现出随机迁移，但不具有趋化性。MEK [丝裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶（ERK）激酶]抑制剂（PD98059和U0126）和磷脂酰肌醇3-激酶（PI3K）抑制剂（渥曼青霉素）可抑制中性粒细胞运动增强和形态学变化，但p38 MAPK抑制剂（SB 203580）不抑制。这些发现与G-CSF选择性激活中性粒细胞中的MEK/ERK和PI3K而不是p38的事实一致。MEK/ERK激活与G-CSF诱导的F-肌动蛋白和磷酸化肌球蛋白轻链的重新分布相关。即使在存在中和性抗CD18抗体的情况下，也观察到中性粒细胞运动性增强，这阻止了细胞粘附。这些结果表明，G-CSF通过激活MEK/ERK和PI3K诱导人中性粒细胞迁移。
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 μm/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.