title: The many facets of SDF-1alpha, CXCR4 agonists and antagonists on hematopoietic progenitor cells.
abstract: Stromal cell-derived factor-1alpha (SDF-1alpha) has pleiotropic effects on hematopoietic progenitor cells (HPCs). We have monitored podia formation, migration, proliferation, and cell-cell adhesion of human HPC under the influence of SDF-1alpha, a peptide agonist of CXCR4 (CTCE-0214), a peptide antagonist (CTCE-9908), and a nonpeptide antagonist (AMD3100). Whereas SDF-1alpha induced migration of CD34(+) cells in a dose-dependent manner, CTCE-0214, CTCE-9908, and AMD3100 did not induce chemotaxis in this concentration range albeit the peptides CTCE-0214 and CTCE-9908 increased podia formation. Cell-cell adhesion of HPC to human mesenchymal stromal cells was impaired by the addition of SDF-1alpha, CTCE-0214, and AMD3100. Proliferation was not affected by SDF-1alpha or its analogs. Surface antigen detection of CXCR4 was reduced upon treatment with SDF-1alpha or AMD3100 and it was enhanced by CTCE-9908. Despite the fact that all these molecules target the same CXCR4 receptor, CXCR4 agonists and antagonists have selective effects on different functions of the natural molecule.
authors.affiliation: Department of Medicine V, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Faber
authors.forename: Christoph
authors.initials: C
authors.lastname: Roderburg
authors.forename: Frederik
authors.initials: F
authors.lastname: Wein
authors.forename: Rainer
authors.initials: R
authors.lastname: Saffrich
authors.forename: Anja
authors.initials: A
authors.lastname: Seckinger
authors.forename: Kerstin
authors.initials: K
authors.lastname: Horsch
authors.forename: Anke
authors.initials: A
authors.lastname: Diehlmann
authors.forename: Donald
authors.initials: D
authors.lastname: Wong
authors.forename: Gary
authors.initials: G
authors.lastname: Bridger
authors.forename: Volker
authors.initials: V
authors.lastname: Eckstein
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagner