Cell surface peptidase CD26/DPPIV mediates G-CSF mobilization of mouse progenitor cells

Kent W. Christopherson, Scott Cooper, Hal Broxmeyer

Research output: Contribution to journalArticle

163 Citations (Scopus)

Abstract

CXC ligand 12 (CXCL12; also known as stromal cell-derived factor 1α/SDF-1α) chemoattracts hematopoietic stem and progenitor cells (HSCs/HPCs) and is thought to play a crucial role in the mobilization of HSCs/HPCs from the bone marrow. CD26 (dipeptidylpeptidase IV [DPPIV]) is a membrane-bound extracellular peptidase that cleaves dipeptides from the N-terminus of polypeptide chains. CD26 has the ability to cleave CXCL12 at its position-2 proline. We found by flow cytometry that CD26 is expressed on a subpopulation of normal Sca-1+c-kit+lin- hematopoietic cells isolated from mouse bone marrow, as well as Sca-1+c-kit-lin- cells, and that these cells possess CD26 peptidase activity. To test the functional role of CD26 in CXCL12-mediated normal HSC/HPC migration, chemotaxis assays were performed. The CD26 truncated CXCL12(3-68) showed an inability to induce the migration of sorted Sca-1+c-kit-lin- or Sca-1+c-kit-lin- mouse marrow cells compared with the normal CXCL12. In addition, CXCL12(3-68) acts as an antagonist, resulting in the reduction of migratory response to normal CXCL12. Treatment of Sca-1+c-kit+lin- mouse marrow cells, and myeloid progenitors within this population, or Sca-1+c-kit-lin- cells with a specific CD26 inhibitor, enhanced the migratory response of these cells to CXCL12. Finally, to test for potential in vivo relevance of these in vitro observations, mice were treated with CD26 inhibitors during granulocyte colony-stimulating factor (G-CSF)-induced mobilization. This treatment resulted in a reduction in the number of progenitor cells in the periphery as compared with the G-CSF regimen alone. This suggests that a mechanism of action of G-CSF mobilization involves CD26.

Original languageEnglish
Pages (from-to)4680-4686
Number of pages7
JournalBlood
Volume101
Issue number12
StatePublished - Jun 15 2003

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Granulocyte Colony-Stimulating Factor
Peptide Hydrolases
Stem Cells
Bone
Bone Marrow
Cells
Chemokine CXCL12
Flow cytometry
Dipeptides
Hematopoietic Stem Cells
Proline
Assays
Ligands
Membranes
Myeloid Progenitor Cells
Peptides
Aptitude
Chemotaxis
Flow Cytometry
Therapeutics

ASJC Scopus subject areas

  • Hematology

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Cell surface peptidase CD26/DPPIV mediates G-CSF mobilization of mouse progenitor cells. / Christopherson, Kent W.; Cooper, Scott; Broxmeyer, Hal.

In: Blood, Vol. 101, No. 12, 15.06.2003, p. 4680-4686.

Research output: Contribution to journalArticle

Christopherson, KW, Cooper, S & Broxmeyer, H 2003, 'Cell surface peptidase CD26/DPPIV mediates G-CSF mobilization of mouse progenitor cells', Blood, vol. 101, no. 12, pp. 4680-4686.
Christopherson, Kent W. ; Cooper, Scott ; Broxmeyer, Hal. / Cell surface peptidase CD26/DPPIV mediates G-CSF mobilization of mouse progenitor cells. In: Blood. 2003 ; Vol. 101, No. 12. pp. 4680-4686.
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