AMD3100 and CD26 modulate mobilization, engraftment, and survival of hematopoietic stem and progenitor cells mediated by the SDF-1/CXCL12-CXCR4 axis

Hal Broxmeyer, Giao Hangoc, Scott Cooper, Timothy Campbell, Shigeki Ito, Charlie Mantel

Research output: Chapter in Book/Report/Conference proceedingConference contribution

61 Citations (Scopus)

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 languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
Pages1-19
Number of pages19
Volume1106
DOIs
StatePublished - Jun 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1106
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

diprotin A
Hematopoietic Stem Cells
Cells
CXCR4 Receptors
Macrophage Inflammatory Proteins
Chemokine CXCL12
CC Chemokines
Granulocyte Colony-Stimulating Factor
Chemokines
Intercellular Signaling Peptides and Proteins
Bone
Blood
Modulation
Ligands
Cell Cycle Proteins
Hematopoiesis
Proteins
Bone Marrow Cells
Cell Survival
Stem Cells

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

Broxmeyer, H., Hangoc, G., Cooper, S., Campbell, T., Ito, S., & Mantel, C. (2007). AMD3100 and CD26 modulate mobilization, engraftment, and survival of hematopoietic stem and progenitor cells mediated by the SDF-1/CXCL12-CXCR4 axis. In Annals of the New York Academy of Sciences (Vol. 1106, pp. 1-19). (Annals of the New York Academy of Sciences; Vol. 1106). https://doi.org/10.1196/annals.1392.013

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 proceedingConference contribution

Broxmeyer, H, Hangoc, G, Cooper, S, Campbell, T, Ito, S & Mantel, C 2007, AMD3100 and CD26 modulate mobilization, engraftment, and survival of hematopoietic stem and progenitor cells mediated by the SDF-1/CXCL12-CXCR4 axis. in Annals of the New York Academy of Sciences. vol. 1106, Annals of the New York Academy of Sciences, vol. 1106, pp. 1-19. https://doi.org/10.1196/annals.1392.013
Broxmeyer H, Hangoc G, Cooper S, Campbell T, Ito S, Mantel C. AMD3100 and CD26 modulate mobilization, engraftment, and survival of hematopoietic stem and progenitor cells mediated by the SDF-1/CXCL12-CXCR4 axis. In Annals of the New York Academy of Sciences. Vol. 1106. 2007. p. 1-19. (Annals of the New York Academy of Sciences). https://doi.org/10.1196/annals.1392.013
Broxmeyer, Hal ; Hangoc, Giao ; Cooper, Scott ; Campbell, Timothy ; Ito, Shigeki ; Mantel, Charlie. / AMD3100 and CD26 modulate mobilization, engraftment, and survival of hematopoietic stem and progenitor cells mediated by the SDF-1/CXCL12-CXCR4 axis. Annals of the New York Academy of Sciences. Vol. 1106 2007. pp. 1-19 (Annals of the New York Academy of Sciences).
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