In vivo effects of recombinant human granulocyte colony-stimulating factor on neutrophil oxidative functions in normal human volunteers

The effect of daily in vivo granulocyte colony-stimulating factor (G-CSF) treatment on neutrophil function was studied over a 14-day period using a luminescence system for differential measurement of oxidase and myeloperoxidase (MPO) dioxygenation activities in whole blood. Opsonin receptor-mediated phagocyte functions were also measured with this system, G-CSF produced a dose-dependent neutrophil leukocytosis and a proportional increase in oxidase activity per volume of blood. The oxidase activity per neutrophil remained relatively constant throughout the test period. However, both chemical- and opsonin-stimulated MPO oxygenation activities per neutrophil were greatly increased by treatment with maxima correlating temporally to initial G-CSF exposure during the early mitotic phase of neutrophil development. The possibility that peroxynitrite contributes to this maximum luminol-dependent activity was tested, but neither superoxide dismutase, a competitive inhibitor of peroxynitrite production, nor N-methyl-L-arginine, an inhibitor of nitric oxide synthase, exerted a significant inhibitory effect.