A novel function of granulocyte colony-stimulating factor in mobilization of human hematopoietic progenitor cells.
Granulocyte colony-stimulating factor (G-CSF) is a common inducer of the release of hematopoietic progenitor cells (HPC) from the bone marrow into the peripheral blood. However, the molecular mechanisms underlying this action of G-CSF have not been fully elucidated. Herein, we demonstrate that G-CSF is a powerful chemotactic agent for human HPC other than modulating the adhesion molecules expressed on HPC or bone marrow stromal cells. G-CSF directly chemoattracted HPC in transwell assay and this chemotaxis is time dependent and is specifically neutralized with antibodies that target its receptor. The number of cells transmigrated through the transwell toward G-CSF stimuli was more than that of stromal cell-derived factor-1 at every concentration. G-CSF induced a rapid, transient increase in F-actin polymerization and the formation of focal contact rings in HPC, which are prerequisites for cell migration. The mechanism of G-CSF-induced chemotaxis appears to involve the phosphorylation of JAK1/STAT3 pathway. Collectively, these results provide evidence that G-CSF promotes chemotactic functionality and suggests new avenues of investigation relevant to the mobilization of HPC.
Zhang
Yun
Y
Department of Immunology, The Fourth Military Medical University, Xi'an, China.
Cheng
Guang
G
Yang
Kun
K
Fan
Rong
R
Xu
Zhuwei
Z
Chen
Lihua
L
Li
Qi
Q
Yang
Angang
A
Jin
Boquan
B
D000199:Actins / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects*; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D053613:Janus Kinase 1 / Q000378:metabolism; D018613:Microscopy, Confocal; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000378:metabolism
D000199:Actins; D018952:Antigens, CD34; D054377:Chemokine CXCL12; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016179:Granulocyte Colony-Stimulating Factor; C507904:JAK1 protein, human; D053613:Janus Kinase 1