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.
Allen
R C
RC
Department of Medicine, University of Washington, and Puget Sound Blood Center, Seattle, USA.
Stevens
P R
PR
Price
T H
TH
Chatta
G S
GS
Dale
D C
DC
D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009895:Opsonin Proteins / Q000494:pharmacology; D010088:Oxidoreductases / Q000097:blood; D009195:Peroxidase / Q000097:blood; D010587:Phagocytosis / Q000187:drug effects; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D009895:Opsonin Proteins; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C091196:opsonin receptor; D016179:Granulocyte Colony-Stimulating Factor; D010088:Oxidoreductases; D009195:Peroxidase