RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (CSF), BUT NOT RECOMBINANT HUMAN GRANULOCYTE CSF, DOWN-REGULATES THE RECOMBINANT HUMAN STEM-CELL FACTOR-DEPENDENT DIFFERENTIATION OF HUMAN FETAL LIVER-DERIVED MAST-CELLS

The effects of recombinant human granulocyte CSF (rhG-CSF) and recombi nant human granulocyte-macrophage CSF (rhGM-CSF) on the recombinant hu man stem cell factor (rhSCF)-dependent development of human mast cells from fetal liver progenitors were examined, Mast cells were identifie d by immunohistochemical staining for tryptase and by flow cytometric analysis of surface Kit expression, Only rhGM-CSF affected mast cell d evelopment, When rhGM-CSF (1, 10, or 100 ng/ml) and rhSCF (50 ng/ml) w ere added to cell cultures from day 0, both the percentage and absolut e numbers of mast cells were diminished after 4 wk compared with cultu res exposed to rhSCF alone, Half of the maximal response was achieved at a dose of rhGM-CSF between 0.1 and 1 ng/ml, The Kit(+) cells develo ping in the presence of rhGM-CSF and rhSCF exhibited an intensity of s urface Kit expression comparable to that of cells exposed to rhSCF alo ne, Also, if the initial exposure to rhGM-CSF was delayed for 1 to 3 w k, attenuation of mast cell development waned, These findings are cons istent with uncommitted progenitor cells being diverted to nonmast cel l lineages by rhGM-CSF, while cells committed to a mast cell lineage, albeit immature, appear to be resistant to the lineage directives of r hCM-CSF, Exposure of fetal liver cells to rhCM-CSF for 1 to 3 days bef ore addition of rhSCF further diminishes the number of mast cells that develop compared with the simultaneous addition of these growth facto rs on day 0, Whether administration of rhCM-CSF to humans before or to gether with rhSCF diminishes the mast cell hyperplasia that occurs wit h rhSCF alone remains to be determined.