Granulocyte-macrophage colony-stimulating factor suppresses induction of neutrophil alkaline phosphatase synthesis by granulocyte colony-stimulating factor

We evaluated the in vitro effects of recombinant human (rh) granulocyte colony-stimulating factor (G-CSF) and rh granulocyte-macrophage CSF (GM-CSF) on neutrophil alkaline phosphatase (NAP) activity and the incorporation of amino acids into polymorphonuclear leukocytes (PMN) from normal individuals and patients with chronic myelogenous leukemia (CML). Both the NAP activity and incorporation of amino acids into PMN were enhanced by the addition of G-CSF in a dose-dependent manner. NAP activity induced by G-CSF in PMN from CML patients showed a greater increase than that in PMN from normal controls. In contrast to G-CSF, GM-CSF did not affect the NAP activity in PMN in spite of the enhanced incorporation of amino acids into PMN by GM-CSF. Interestingly, both the NAP-inducing ability of G-CSF and its enhancing ability for amino acid incorporation were suppressed by GM-CSF in a dose-dependent manner when PMN were incubated with various concentrations of GM-CSF in addition to 100 ng/ml of G-CSF. These observations suggest that G-CSF and GM-CSF act differently: G-CSF induces NAP synthesis in PMN, whereas GM-CSF negatively modulates the effect of G-CSF. Further, it is suggested that protein synthesis induced by G-CSF is negatively modulated by GM-CSF in a general fashion.