The Many Facets of SDF-1α, CXCR4 Agonists and Antagonists on Hematopoietic Progenitor Cells
Anne Faber,1 Christoph Roderburg,1 Frederik Wein,1 Rainer Saffrich,1 Anja Seckinger,1 Kerstin Horsch,1 Anke Diehlmann,1 Donald Wong,2 Gary Bridger,3 Volker Eckstein,1 Anthony D. Ho,1 and Wolfgang Wagner1,4
1 Department of Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, Heidelberg 69120, Germany
2 Chemokine Therapeutics Corporation, 6190 Agronomy Road, Vancouver V6T 1Z3, BC, Canada
3 AnorMED, 20353 64th Avenue, Langley V2Y 1N5, BC, Canada
4 Department of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, Heidelberg 69120, Germany
Stromal cell-derived factor-1alpha (SDF-1α) 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-1α, a peptide agonist of CXCR4 (CTCE-0214), a peptide antagonist (CTCE-9908), and a nonpeptide antagonist (AMD3100). Whereas SDF-1α 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-1α, CTCE-0214, and AMD3100. Proliferation was not affected by SDF-1α or its analogs. Surface antigen detection of CXCR4 was reduced upon treatment with SDF-1α 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.
Journal of Biomedicine and Biotechnology Volume 2007 (2007), Article ID 26065, 10 pages. doi:10.1155/2007/26065.