Cell surface peptidase CD26/dipeptidylpeptidase IV regulates CXCL12/stromal cell-derived factor-1α-mediated chemotaxis of human cord blood CD34+ progenitor cells

Kent W. Christopherson, Giao Hangoc, Hal Broxmeyer

Research output: Contribution to journalArticle

218 Citations (Scopus)

Abstract

CD26/dipeptidylpeptidase IV (DPPIV) is a membrane-bound extracellular peptidase that cleaves dipeptides from the N terminus of polypeptide chains. The N terminus of chemokines is known to interact with the extracellular portion of chemokine receptors, and removal of these amino acids in many instances results in significant changes in functional activity. CD26/DPPIV has the ability to cleave the chemokine CXCL12/stromal cell-derived factor 1α (SDF-1α) at its position two proline. CXCL12/SDF-1α induces migration of hemopoietic stem and progenitor cells, and it is thought that CXCL12 plays a crucial role in homing/mobilization of these cells to/from the bone marrow. We found that CD26/DPPIV is expressed by a subpopulation of CD34+ hemopoietic cells isolated from cord blood and that these cells have DPPIV activity. The involvement of CD26/DPPIV in CD34+ hemopoietic stem and progenitor cell migration has not been previously examined. Functional studies show that the N-terminal-truncated CXCL12/SDF-1α lacks the ability to induce the migration of CD34+ cord blood cells and acts to inhibit normal CXCL12/SDF-1α-induced migration. Finally, inhibiting the endogenous CD26/DPPIV activity on CD34+ cells enhances the migratory response of these cells to CXCL12/SDF-1α. This process of CXCL12/SDF-1α cleavage by CD26/DPPIV on a subpopulation of CD34+ cells may represent a novel regulatory mechanism in hemopoietic stem and progenitor cells for the migration, homing, and mobilization of these cells. Inhibition of the CD26/DPPIV peptidase activity may therefore represent an innovative approach to increasing homing and engraftment during cord blood transplantation.

Original languageEnglish
Pages (from-to)7000-7008
Number of pages9
JournalJournal of Immunology
Volume169
Issue number12
StatePublished - Dec 15 2002

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Chemokine CXCL12
Chemotaxis
Fetal Blood
Peptide Hydrolases
Stem Cells
Aptitude
Cell Movement
Blood Cells
Dipeptides
Chemokine Receptors
Chemokines
Proline
Bone Marrow Cells
Transplantation
Amino Acids
Peptides
Membranes

ASJC Scopus subject areas

  • Immunology

Cite this

Cell surface peptidase CD26/dipeptidylpeptidase IV regulates CXCL12/stromal cell-derived factor-1α-mediated chemotaxis of human cord blood CD34+ progenitor cells. / Christopherson, Kent W.; Hangoc, Giao; Broxmeyer, Hal.

In: Journal of Immunology, Vol. 169, No. 12, 15.12.2002, p. 7000-7008.

Research output: Contribution to journalArticle

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abstract = "CD26/dipeptidylpeptidase IV (DPPIV) is a membrane-bound extracellular peptidase that cleaves dipeptides from the N terminus of polypeptide chains. The N terminus of chemokines is known to interact with the extracellular portion of chemokine receptors, and removal of these amino acids in many instances results in significant changes in functional activity. CD26/DPPIV has the ability to cleave the chemokine CXCL12/stromal cell-derived factor 1α (SDF-1α) at its position two proline. CXCL12/SDF-1α induces migration of hemopoietic stem and progenitor cells, and it is thought that CXCL12 plays a crucial role in homing/mobilization of these cells to/from the bone marrow. We found that CD26/DPPIV is expressed by a subpopulation of CD34+ hemopoietic cells isolated from cord blood and that these cells have DPPIV activity. The involvement of CD26/DPPIV in CD34+ hemopoietic stem and progenitor cell migration has not been previously examined. Functional studies show that the N-terminal-truncated CXCL12/SDF-1α lacks the ability to induce the migration of CD34+ cord blood cells and acts to inhibit normal CXCL12/SDF-1α-induced migration. Finally, inhibiting the endogenous CD26/DPPIV activity on CD34+ cells enhances the migratory response of these cells to CXCL12/SDF-1α. This process of CXCL12/SDF-1α cleavage by CD26/DPPIV on a subpopulation of CD34+ cells may represent a novel regulatory mechanism in hemopoietic stem and progenitor cells for the migration, homing, and mobilization of these cells. Inhibition of the CD26/DPPIV peptidase activity may therefore represent an innovative approach to increasing homing and engraftment during cord blood transplantation.",
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