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 oxi dase in mature myeloid cells, we isolated neutrophils from patients re ceiving recombinant human granulocyte colony stimulating factor (G-CSF ) and recombinant human stem cell factor (SCF) and evaluated oxidase a ctivity. All patients had relapsed neoplastic disease and were at leas t 3 three weeks since the last course of chemotherapy or cytokine ther apy. Methods: Stimulus induced superoxide anion (O-2(-)) production in response to PMA (200 ng/mL), fMLP (1 mu mol/L), platelet activating f actor (PAF, 2 mu mol/L) priming of the fMLP induced response, and opso nized 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 act ivity was assessed in an SDS cell-free system. Results: SCF had no eff ect on the activity of the neutrophil oxidase, Neutrophils isolated fr om patients treated with G-CSF and stimulated with PMA produced less ( superoxide anion) O-2(-) after therapy. PAF priming of the fMLP induce d respiratory burst was also reduced after therapy with G-CSF, Subcell ular NADPH oxidase activity was reduced before cytokine therapy commen ced, This activity did not improve with cytokine treatment. Conclusion s: It appears likely from this study that G-CSF therapy, with or witho ut SCF, does not cause significant enhancement of neutrophil NADPH oxi dase activity.