Recruitment of primitive peripheral blood cells: Synergism of interleukin 12 with interleukin 6 and stromal cell-derived factor-1

In bone marrow, haematopoietic stem cells (HSC) rely On close contact with stromal cells for proliferation and differentiation. Stromal cell-derived f actor (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 evaluate d for effects oh proliferation of both mature and immature human progenitor cells in vitro. Neither proliferation nor maturation of peripheral blood c ells was stimulated by SDF-1 alone. Moreover, we have previously demonstrat ed that 5-fluorouracile (5-FU) resistant HSC require a combination of inter leukin 12 (IL-12), IL-6 and SCF for the production of morphologically recog nizable clonogenic elements at day 14 in semisolid medium. Our data reporte d 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 syn ergistic effects in combination with early-acting cytokines, These results suggest that a programmed response to sequential cytokine stimulation may b e part of a control mechanism required for maintenance of proliferation of primitive HSC. (C) 2000 Academic press.