In Vitro Study of the Independent and Combined Effects of Recombinant Human GM-CSF and G-CSF on Normal Bone Marrow Granulocytes : GM-CSF Enhances the Growth Effect but Suppresses the Terminal Maturation-inducing Effect of G-CSF

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We studied the independent and combined effects of recombinant human granulocyte colony- stimularting factor (rhG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the growth and maturation of neutrophilic granulocytes. Absolute granulocyte numbers, cellular composition, and neutrophil alkailne phosphatase (NAP) activity were examined after normal nonphagocytic bone marrow cells were cultured for seven days with rhG-CSF, rhGM-CSF, and a combination of both growth factors. The numbers of band and segmented forms produced in the cultures containing rhGM-CSF were significantly lower than in control cultures or those with rhG-CSF. When both rhGM-CSF and rhG-CSF were in the culture total granulocyte production was highest, but the increment of band and segmented forms produced by rhG-CSF alone was reduced. Neutrophil alkaline phosphatase (NAP), an enzyme marking terminal maturation, was increased by rhG-CSF alone, but not by rhGM-CSF alone. Cultures containing both CSFs showed significantly lowered NAP activity compared to those containing rhG-CSF alone. The decrement in NAP activity was proportionate to the amount of rhGM-CSF added. These results indicate that terminal maturation-inducing effect is a property of rhG-CSF but not of rhGM-CSF. In the presence of both GM-CSF and G-CSF, the growth of granulocytes is maximumly stimulated but the terminal maturation-inducing effect of rhG-CSF is suppressed.
1990-12-14