Abstract
The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) and its receptor, CXCR4, are involved in a number of facets of the regulation of hematopoiesis at the level of hematopoietic stem (HSCs) and progenitor (HPCs) cells. Modulation of this ligand-receptor interaction may be of clinical utility.We now report that: (1) the CC chemokine, macrophage inflammatory protein-1α (MIP-1α/CCL3) synergizes with AMD3100 (an antagonist of the binding of SDF-1/CXCL12 to CXCR4) to rapidly mobilize HPCs to the blood of mice; moreover, the combination of granulocyte colony-stimulating factor (G-CSF) with AMD3100 and MIP-1α/CCL3, given in a specific sequence, mobilizes the greatest number of HPCs compared to any combination of two of these mobilizing agents; (2) pretreatment of recipient mice with Diprotin A, an inhibitor of CD26/Dipeptidylpeptidase IV (DPPIV), enhances the competitive HSCs repopulating capacity of untreated donor cells; (3) the survival-enhancing effects of SDF-1/CXCL12 on HPCs subjected in vitro to delayed addition of growth factors (GFs) are mediated in part through the cell cycle-related proteins p21 cip1/waf1 (as assessed using p21cip1/waf1 ?/? and +/+ mice) and Mad2 (using Mad2 +/? and +/+ mice); and (4) deletion of CD26/DPPIV on mouse bone marrow cells increases the survival-enhancing effects of SDF-1/CXCL12 on HPCs. These results demonstrate the means to increase the mobilization of HPCs, the engrafting capability of HSCs, and responsiveness of HPCs to the survival-enhancing activity of SDF-1/CXCL12, effects that may be of practical value.
| Original language | English |
|---|---|
| Title of host publication | Annals of the New York Academy of Sciences |
| Pages | 1-19 |
| Number of pages | 19 |
| Volume | 1106 |
| DOIs | |
| State | Published - Jun 2007 |
Publication series
| Name | Annals of the New York Academy of Sciences |
|---|---|
| Volume | 1106 |
| ISSN (Print) | 00778923 |
| ISSN (Electronic) | 17496632 |
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Keywords
- AMD3100
- CD26/DPPIV
- CXCR4
- Hematopoietic stem cells
- Progenitor cells
- SDF-1/CXCL12
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
AMD3100 and CD26 modulate mobilization, engraftment, and survival of hematopoietic stem and progenitor cells mediated by the SDF-1/CXCL12-CXCR4 axis. / Broxmeyer, Hal; Hangoc, Giao; Cooper, Scott; Campbell, Timothy; Ito, Shigeki; Mantel, Charlie.
Annals of the New York Academy of Sciences. Vol. 1106 2007. p. 1-19 (Annals of the New York Academy of Sciences; Vol. 1106).Research output: Chapter in Book/Report/Conference proceeding › Conference contribution
}
TY - GEN
T1 - AMD3100 and CD26 modulate mobilization, engraftment, and survival of hematopoietic stem and progenitor cells mediated by the SDF-1/CXCL12-CXCR4 axis
AU - Broxmeyer, Hal
AU - Hangoc, Giao
AU - Cooper, Scott
AU - Campbell, Timothy
AU - Ito, Shigeki
AU - Mantel, Charlie
PY - 2007/6
Y1 - 2007/6
N2 - The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) and its receptor, CXCR4, are involved in a number of facets of the regulation of hematopoiesis at the level of hematopoietic stem (HSCs) and progenitor (HPCs) cells. Modulation of this ligand-receptor interaction may be of clinical utility.We now report that: (1) the CC chemokine, macrophage inflammatory protein-1α (MIP-1α/CCL3) synergizes with AMD3100 (an antagonist of the binding of SDF-1/CXCL12 to CXCR4) to rapidly mobilize HPCs to the blood of mice; moreover, the combination of granulocyte colony-stimulating factor (G-CSF) with AMD3100 and MIP-1α/CCL3, given in a specific sequence, mobilizes the greatest number of HPCs compared to any combination of two of these mobilizing agents; (2) pretreatment of recipient mice with Diprotin A, an inhibitor of CD26/Dipeptidylpeptidase IV (DPPIV), enhances the competitive HSCs repopulating capacity of untreated donor cells; (3) the survival-enhancing effects of SDF-1/CXCL12 on HPCs subjected in vitro to delayed addition of growth factors (GFs) are mediated in part through the cell cycle-related proteins p21 cip1/waf1 (as assessed using p21cip1/waf1 ?/? and +/+ mice) and Mad2 (using Mad2 +/? and +/+ mice); and (4) deletion of CD26/DPPIV on mouse bone marrow cells increases the survival-enhancing effects of SDF-1/CXCL12 on HPCs. These results demonstrate the means to increase the mobilization of HPCs, the engrafting capability of HSCs, and responsiveness of HPCs to the survival-enhancing activity of SDF-1/CXCL12, effects that may be of practical value.
AB - The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) and its receptor, CXCR4, are involved in a number of facets of the regulation of hematopoiesis at the level of hematopoietic stem (HSCs) and progenitor (HPCs) cells. Modulation of this ligand-receptor interaction may be of clinical utility.We now report that: (1) the CC chemokine, macrophage inflammatory protein-1α (MIP-1α/CCL3) synergizes with AMD3100 (an antagonist of the binding of SDF-1/CXCL12 to CXCR4) to rapidly mobilize HPCs to the blood of mice; moreover, the combination of granulocyte colony-stimulating factor (G-CSF) with AMD3100 and MIP-1α/CCL3, given in a specific sequence, mobilizes the greatest number of HPCs compared to any combination of two of these mobilizing agents; (2) pretreatment of recipient mice with Diprotin A, an inhibitor of CD26/Dipeptidylpeptidase IV (DPPIV), enhances the competitive HSCs repopulating capacity of untreated donor cells; (3) the survival-enhancing effects of SDF-1/CXCL12 on HPCs subjected in vitro to delayed addition of growth factors (GFs) are mediated in part through the cell cycle-related proteins p21 cip1/waf1 (as assessed using p21cip1/waf1 ?/? and +/+ mice) and Mad2 (using Mad2 +/? and +/+ mice); and (4) deletion of CD26/DPPIV on mouse bone marrow cells increases the survival-enhancing effects of SDF-1/CXCL12 on HPCs. These results demonstrate the means to increase the mobilization of HPCs, the engrafting capability of HSCs, and responsiveness of HPCs to the survival-enhancing activity of SDF-1/CXCL12, effects that may be of practical value.
KW - AMD3100
KW - CD26/DPPIV
KW - CXCR4
KW - Hematopoietic stem cells
KW - Progenitor cells
KW - SDF-1/CXCL12
UR - http://www.scopus.com/inward/record.url?scp=34548437672&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548437672&partnerID=8YFLogxK
U2 - 10.1196/annals.1392.013
DO - 10.1196/annals.1392.013
M3 - Conference contribution
C2 - 17360804
AN - SCOPUS:34548437672
SN - 1573316768
SN - 9781573316767
VL - 1106
T3 - Annals of the New York Academy of Sciences
SP - 1
EP - 19
BT - Annals of the New York Academy of Sciences
ER -