The many facets of SDF-1alpha, CXCR4 agonists and antagonists on hematopoietic progenitor cells.
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.
Faber
Anne
A
Department of Medicine V, University of Heidelberg, 69120 Heidelberg, Germany.
Roderburg
Christoph
C
Wein
Frederik
F
Saffrich
Rainer
R
Seckinger
Anja
A
Horsch
Kerstin
K
Diehlmann
Anke
A
Wong
Donald
D
Bridger
Gary
G
Eckstein
Volker
V
Ho
Anthony D
AD
Wagner
Wolfgang
W