Recombinant human granulocyte colony-stimulating factor (rhG-CSF) enhanced superoxide (O-2) release and membrane depolarization in human neutrophils stimulated by the receptor-mediated agonists, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and wheat germ agglutinin, but not by the Ca2+ ionophore ionomycin and phorbol myristate acetate, which bypass the receptors to stimulate the cells. The optimal effect was obtained by pretreatment of cells with 25-50ng/ml rhG-CSF for 10min at 37°C. rhG-CSF neither affected stimulus-induced increase in cytoplasmic free Ca2+ nor changed the number and affinity of FMLP-receptors. rhG-CSF increased the expression of C3bi-receptors on human neutrophils and enhanced adherence to nylon fiber.
rhG-CSF was administered (50-800μg/m2) once daily as a half-hour intravenous infusion for a total of 14 days to seven patients with malignant lymphoma following the treatment with cytotoxic drugs. In all patients, the administration of rhG-CSF not only increased the peripheral blood neutrophil count and reduced the periods of neutropenia but also enhanced O-2 release in neutrophils stimulated by FMLP. The administration of rhG-CSF also rapidly caused an increase in the expression of neutrophil C3bi-receptors. The pharmacokinetic study of rhG-CSF gave the half-life of 114min. These findings demonstrate that rhG-CSF is a potent activator for neutrophil functions in vivo as well as in vitro.
