The effects of stem cell factor and granulocyte colony stimulating factor therapy on the activity of the neutrophil NADPH oxidase enzyme system.
BACKGROUND
To explore the effect of cytokine therapy on the NADPH oxidase in mature myeloid cells, we isolated neutrophils from patients receiving recombinant human granulocyte colony stimulating factor (G-CSF) and recombinant human stem cell factor (SCF) and evaluated oxidase activity. All patients had relapsed neoplastic disease and were at least 3 three weeks since the last course of chemotherapy or cytokine therapy.


METHODS
Stimulus induced superoxide anion (O2-) production in response to PMA (200 ng/mL), fMLP (1 mumol/L), platelet activating factor (PAF, 2 mumol/L) priming of the fMLP induced response, and opsonized zymosan OZ (1 mg/mL) was measured. Polymorphonuclear leukocyte (PMN) subcellular components were prepared, after nitrogen cavitation, by separation on discontinuous sucrose gradients and NADPH oxidase activity was assessed in a SDS cell-free system.


RESULTS
SCF had no effect on the activity of the neutrophil oxidase. Neutrophils isolated from patients treated with G-CSF and stimulated with PMA produced less (superoxide anion) O2- after therapy. PAF priming of the fMLP induced respiratory burst was also reduced after therapy with G-CSF. Subcellular NADPH oxidase activity was reduced before cytokine therapy commenced. This activity did not improve with cytokine treatment.


CONCLUSIONS
It appears likely from this study that G-CSF therapy, with or without SCF, does not cause significant enhancement of neutrophil NADPH oxidase activity.
Leavey
P J
PJ
Bonfils Blood Center, Denver, CO, USA.
Thurman
G
G
Gonzalez-Aller
C
C
Zerbe
G
G
Ambruso
D R
DR
D000328:Adult; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019255:NADPH Oxidases / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D019089:Stem Cell Factor / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate