Differential activity of recombinant colony-stimulating factors in supporting proliferation of human peripheral blood and bone marrow myeloid progenitors in culture.

Unlike bone marrow progenitor cells, human myeloid progenitors isolated from peripheral blood do not form colonies in semi-solid medium in the presence of rhG-CSF, rhM-CSF or rhIL-6, but do form colonies containing neutrophils, macrophages, eosinophils, basophils or mixed neutrophilic-macrophages colonies in the presence of rhIL-3 or rhGM-CSF. Priming of blood progenitors by culturing them for several days in the presence of rhGM-CSF resulted in a dramatic increase in the frequency of cells that proliferate in response to G-CSF and IL-6 and form neutrophilic granulocytic colonies. Suspension cultures maintained in the presence of IL-3 yielded increased numbers of clonogenic cells responsive to GM-CSF and G-CSF, but not to M-CSF or IL-6. rhIL-6 did not directly stimulate colony formation of peripheral blood progenitors but did prime them to respond to G-CSF. These results are consistent with a hierarchical model of granulocytic differentiation in which circulating progenitors proceed sequentially through a programme of changing growth factor sensitivity with the following sequence: IL-3, GM-CSF, IL-6 and/or G-CSF.