title: Cytokine combinations differentially influence the SDF-1alpha-dependent migratory activity of cultivated murine hematopoietic stem and progenitor cells.
abstract: Stromal cell-derived factor-1alpha (SDF-1alpha) is a strong migratory stimulant for hematopoietic stem and progenitor cells (HSPCs). The hematopoietic cytokines thrombopoietin (TPO), Flt3-ligand (FL), stem cell factor (SCF) and interleukin 11 (IL-11) are able to stimulate amplification of primitive murine hematopoietic stem cells (HSCs) in vitro. The effects of these cytokines on SDF-1alpha-induced migratory activity of murine Lin(-)c-kit+ HSPC were analyzed by cultivation of these cells in the presence of 12 combinations of FL, TPO, SCF and IL-11. Migratory activity was measured in a three-dimensional collagen matrix using time-lapse video microscopy. Each cytokine combination had a distinct effect on SDF-1alpha-stimulated migratory activity. For instance, FL- and SCF-cultivated cells showed a high migratory SDF-1alpha response, while cells cultivated with SCF, TPO and IL-11 did not react to SDF-1alpha stimulation with an elevated migration rate. Our data indicate that the differences in the migratory SDF-1alpha response are not related to different CXCR4 expression levels, but rather to the differential engagement of the CXCR4-dependent MAPK p42/44 and PI3K signal transduction pathways. This indicates that hematopoietic cytokines can have a significant impact on SDF-1alpha-stimulated migratory activity and the underlying intracellular signaling processes in cultivated HSPCs.
authors.affiliation: Institute of Immunology, Witten/Herdecke University, Stockumer Strasse 10, Witten, Germany.
authors.forename: Susannah H
authors.initials: SH
authors.lastname: Kassmer
authors.forename: Bernd
authors.initials: B
authors.lastname: Niggemann
authors.forename: Michael
authors.initials: M
authors.lastname: Punzel
authors.forename: Christine
authors.initials: C
authors.lastname: Mieck
authors.forename: Kurt S
authors.initials: KS
authors.lastname: Zänker
authors.forename: Thomas
authors.initials: T
authors.lastname: Dittmar
mesh_terms: D000818:Animals; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D003470:Culture Media; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects*
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D003470:Culture Media; D016207:Cytokines; D019718:Receptors, CXCR4