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  • 1
    ISSN: 1573-8280
    Keywords: C-kit Ligand ; GM-CSF ; Hemopoiesis ; IL-3 ; MGF ; Myelosuppression ; Radiation ; SCF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the presence of hemopoietic cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), mast cell growth factor (MGF; also known as steel factor, stem cell factor, and c-kit ligand) has proven to be a potent hemopoietic regulatorin vitro. In these studies, we examined thein vivo effects of MGF in combination with GM-CSF or GM-CSF plus IL-3. Effects were based on the ability of these cytokines to stimulate recovery from radiation-induced hemopoietic aplasia. Female B6D2F1 mice were exposed to a sublethal 7.75-Gy dose of60Co radiation followed by subcutaneous administration of either saline, recombinant murine (rm) MGF (100Μg/kg/day), rmGM-CSF (100Μg/kg/day), rmIL-3 (100Μg/kg/day), or combinations of these cytokines on days 1–17 postirradiation. Recoveries of bone marrow and splenic spleen colony-forming units (CFU-s), granulocyte macrophage colony-forming cells (GM-CFC), and peripheral white blood cells (WBC), red blood cells (RBC) and platelets (PLT) were determined on days 14 and 17 during the postirradiation recovery period. MGF administered in combination with GM-CSF or in combination with GM-CSF plus IL-3 either produced no greater response than GM-CSF alone or down-regulated the GM-CSF-induced recovery. These results sharply contrasted results ofin vitro studies evaluating the effects of these cytokines on induction of GM-CFC colony formation from bone marrow cells obtained from normal or irradiated B6D2F1 mice, in which MGF synergized with GM-CSF or GM-CSF plus IL-3 to increase both GM-CFC colony numbers and colony size. These studies demonstrate a dichotomy between MGF-induced effectsin vivo andin vitro and emphasize that caution should be taken in attempting to predict cytokine interactionsin vivo in hemopoietically injured animals based onin vitro cytokine effects.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0584
    Keywords: Hematopoiesis ; GM-CSF ; IL-3 ; IL-1 ; Precursor cells ; Cytofluorometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Our experiments were directed towards the detection of the influence of interleukin-1 (IL-1); interleukin-3 (IL-3), and granulocyte-macrophage colonystimulating factor (GM-CSF) on the generation of granulocyte-macrophage progenitor cells. We also set out to examine whether this process is connected with changes within the early precursor cell compartment. Bone marrow suspension cultures (12 days) supplemented with these cytokines were tested for the presence of GM colony-forming cells (GM-CFC) in a colony-forming unit assay. The percentage of CD 34+ and HLA-DR+ as well as the number of blasts and promyelocytes were estimated cytofluorometrically and morphologically. The proliferative effect of GM-CSF was associated with a net increase of GM-CFC and HLA-DR+ myeloid cells and a decrease in the percentage of CD 34+ early precursor cells. IL-3 acted similarly and also caused an absolute decrease of CD 34+ cells in the cultures. IL-1 did not stimulate the generation of blasts or GM-CFC but elevated the number of CD 34− as well as HLA-DR-expressing cells in the cultures. These results imply that GM-CSF supported the maintenance of hematopoiesis in vitro. The transition from early precursor cells to committed myeloid progenitor cells (GM-CFC) and more mature precursor cells (G-CFC, M-CFC) may be supported by GM-CSF without affecting the self-renewing capacity of CD 34+ early precursors. In contrast, the blast-generating and proliferation-inducing action of IL-3 is associated with a drop in the total number of CD 34+ stem cells. An efficient renewal of this population obviously depends on the presence of IL-1.
    Type of Medium: Electronic Resource
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