INDUCTION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) AND GRANULOCYTE-COLONY-STIMULATING FACTOR (G-CSF) EXPRESSION IN BONE-MARROW AND FRACTIONATED MARROW CELL-POPULATIONS BY INTERLEUKIN-3 (IL-3) - IL-3-MEDIATED POSITIVE FEEDBACK MECHANISMS OF GRANULOPOIESIS

Interleukin 3 (IL-3) induces proliferation and differentiation of mast cell progenitors in vitro, whereas it induces granulocytosis in vivo. In this paper, a positive feedback mechanism of granulopoiesis was st udied in order to elucidate the granulocytosis induced by IL-3 in mous e. IL-3 induced expression of granulocyte-macrophage colony-stimulatin g factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in total bone marrow cells and a marrow adherent cell population. In fra ctionated marrow cell populations, a different expression pattern of i nduction by IL-3 stimulation was observed; GM-CSF was expressed in mac rophages and fraction 1 (P<1.061) and 2(1.061<P<1.074) of bone marrow cells fractionated by equilibrium density centrifugation, G-CSF was ex pressed in macrophages and fraction 2 and 3 (1.074<P<1.097), and inter leukin 6 (IL-6) in macrophages and fraction 1 to 3. These results indi cate a hierarchical regulation of cytokine production and the existenc e of a positive feedback mechanism in granulopoiesis. IL-6, induced by IL-3, stimulates stem cells into cycle and induces stem cells to resp ond to IL-3. The stem cells differentiate to granulocyte-macrophage co lony-forming cells by the combined effect of IL-3 and IL-6. IL-3 also induces GM- and G-CSF expression which in turn makes granulocyte-macro phage colony-forming cells differentiate to granulocytes. These factor s organize a cytokine network in granulopoiesis.