Enhanced neutrophil motility by granulocyte colony-stimulating factor: the role of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase

Immunology. 2006 Nov;119(3):393-403. doi: 10.1111/j.1365-2567.2006.02448.x. Epub 2006 Aug 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Movement / immunology
  • Cells, Cultured
  • Chemotaxis, Leukocyte / immunology
  • Extracellular Signal-Regulated MAP Kinases / immunology*
  • Granulocyte Colony-Stimulating Factor / immunology*
  • Humans
  • Microscopy, Video
  • Myosin Light Chains / metabolism
  • Neutrophil Activation / immunology
  • Neutrophils / immunology*
  • Phosphatidylinositol 3-Kinases / immunology*
  • Phosphorylation
  • Signal Transduction / immunology


  • Myosin Light Chains
  • Granulocyte Colony-Stimulating Factor
  • Phosphatidylinositol 3-Kinases
  • Extracellular Signal-Regulated MAP Kinases