title: Recruitment of primitive peripheral blood cells: synergism of interleukin 12 with interleukin 6 and stromal cell-derived FACTOR-1.
abstract: In bone marrow, haematopoietic stem cells (HSC) rely on close contact with stromal cells for proliferation and differentiation. Stromal cell-derived factor (SDF-1) is a chemokine produced by bone marrow stromal cells and has been reported to be a chemoattractant for CD34(+)cells. SDF-1 was evaluated for effects on proliferation of both mature and immature human progenitor cells in vitro. Neither proliferation nor maturation of peripheral blood cells was stimulated by SDF-1 alone. Moreover, we have previously demonstrated that 5-fluorouracile (5-FU) resistant HSC require a combination of interleukin 12 (IL-12), IL-6 and SCF for the production of morphologically recognizable clonogenic elements at day 14 in semisolid medium. Our data reported a strong enhancement of the IL-6, IL-12, SCF-induced synergism (172%) by SDF-1 (296.5%). Furthermore, our data suggest that this chemokine alone had no effect on triggering quiescent cells and may preserve these cells from 5-FU cell damage or upregulate early-acting cytokine receptors. Thus, SDF-1 might play a key role in early human haematopoiesis through its potent synergistic effects in combination with early-acting cytokines. These results suggest that a programmed response to sequential cytokine stimulation may be part of a control mechanism required for maintenance of proliferation of primitive HSC.
authors.affiliation: Research Department of Microenvironment and Cell Integrated Renewal (MERCI), 22, Boulevard Gambetta, Rouen Cedex, 76183, France. stephanie.grafte@wanadoo.fr
authors.forename: S
authors.initials: S
authors.lastname: Grafte-Faure
authors.forename: C
authors.initials: C
authors.lastname: Leveque
authors.forename: E
authors.initials: E
authors.lastname: Ketata
authors.forename: P
authors.initials: P
authors.lastname: Jean
authors.forename: M
authors.initials: M
authors.lastname: Vasse
authors.forename: C
authors.initials: C
authors.lastname: Soria
authors.forename: J P
authors.initials: JP
authors.lastname: Vannier
mesh_terms: D000963:Antimetabolites / Q000009:adverse effects; D001773:Blood Cells / Q000166:cytology* / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology*; D016207:Cytokines / Q000502:physiology; D015672:Erythroid Precursor Cells / Q000166:cytology; D005472:Fluorouracil / Q000009:adverse effects; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D018664:Interleukin-12 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects
chemical_list: D000963:Antimetabolites; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016207:Cytokines; D015850:Interleukin-6; D018664:Interleukin-12; D005472:Fluorouracil