[The role of stromal cell-derived factor and its receptor-CXCR4 in G-CSF-induced hematopoietic stem cell mobilization].
OBJECTIVE
To explore the role of stromal cell-derived factor (SDF-1) and its specific receptor CXCR4 in the G-CSF-induced hematopoietic stem/progenitor cells (HSPCs) mobilization in human healthy donor.


METHODS
The changes of SDF-1/CXCR4 in bone marrow (BM) and peripheral blood (PB) of healthy donors during G-CSF-induced mobilization were detected by enzyme-linked immunosorbent assay (ELISA), immunohistological staining and flow cytometry. SDF-1 neutralizing antibody wes injected into BALB/c mice to further test its effect on mobilization.


RESULTS
SDF-1 concentration in mobilized BM (mBM), steady state BM (ssBM) and PB were(7.23 +/- 0.66) microg/L, (5.43 +/- 0.35) microg/L and (5.42 +/- 0.52) microg/L, respectively. SDF-1 protein levels were decreased in the BM (P < 0.05) after 5-day G-CSF injection, and its concentration gradient between BM and PB disappeared (P > 0.05). Significant up-regulation of CXCR4 expression was observed on mBM CD34 cells in healthy donors. The rate of CXCR4 expression on CD34 cells in ssBM, mBM and mobilized PB were (40.98 +/- 21.56)%, (65.80 +/- 24.68)% and (27.54 +/- 26.03)%, respectively. Comparing with that in ssBM and mBM, CXCR4 expression on mobilized PB CD34+ cells were significantly decreased (P < 0.05). Inhibition of SDF-1 signal by blocking monoclonal antibodies significantly reduced G-CSF-induced mobilization in BALB/c mice. This resulted in significant decrease of white blood cell count and progenitors mobilized into peripheral circulation.


CONCLUSIONS
G-CSF induces HSPCs mobilization by decreasing bone marrow SDF-1 and down-regulating CXCR4 expression on HSPCs.
Jin
Feng-Yan
FY
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China.
Qiu
Lu-Gui
LG
Li
Qiao-Chuan
QC
Meng
Heng-Xing
HX
Wang
Ya-Fei
YF
Yu
Zhen
Z
Li
Qian
Q
Han
Jun-Lin
JL
D000818:Animals; D054377:Chemokine CXCL12 / Q000378:metabolism / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D019718:Receptors, CXCR4 / Q000378:metabolism / Q000502:physiology*
D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor