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-C SF) treatment on neutrophil function was studied over a 14-day period using a luminescence system for differential measurement of oxidase an d myeloperoxidase (MPO) dioxygenation activities in whole blood. Opson in 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 oxi dase activity per neutrophil remained relatively constant throughout t he test period. However, both chemical- and opsonin-stimulated MPO oxy genation activities per neutrophil were greatly increased by treatment with maxima correlating temporally to initial G-CSF exposure during t he 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.