CD14(-COLONY-STIMULATING FACTOR (G-CSF)-MOBILIZED PERIPHERAL-BLOOD MONONUCLEAR-CELLS INDUCE SECRETION OF INTERLEUKIN-6 AND G-CSF BY MARROW STROMA() CELLS IN GRANULOCYTE)

The ability of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (G-PBMCs) to induce secretion of c ytokines in primary longterm marrow cultures (LTC) or in the human mar row stromal cell line HS23 was compared with that of marrow mononuclea r cells. Equal numbers of G-PBMCs or marrow mononuclear cells were add ed to stromal cultures, supernatants were harvested at day 4 and level s of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-6, G-CSF, a nd tumor necrosis factor alpha (TNF alpha) were determined. G-PBMCs in duced 21.4-fold higher levels of IL-6 and 12.5-fold higher levels of G -CSF in LTC cocultures compared with marrow mononuclear cells and indu ced 20.6-fold more IL-6 and 6.3-fold more G-CSF when added to HS23 cel ls. Experiments using sorted populations of CD20(+), CD3(+), and CD14( +) cells showed that CD14(+) cells within G-PBMCs were responsible for triggering the production of IL-6 and G-CSF. The effect did not requi re cell-cell contact and was inhibited when neutralizing antibodies to lL-1 alpha and IL-1 beta were used in combination. In these experimen ts, the greater stimulating ability of G-PBMCs is most likely attribut able to the greater number of CD14(+) cells in G-PBMCs (26.1% +/- 2.3% ) compared with marrow (2.5% +/- 0.8%), because equal numbers of CD14( +) cells sorted from marrow and G-PBMCs showed comparable ability to i nduce IL-6 and G-CSF when placed directly on stromal cells. (C) 1996 b y The American Society of Hematology.