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 μmol/L), platelet activating factor (PAF, 2 μmol/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 an 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.