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In vivo activation of human neutrophil functions by administration of
recombinant human granulocyte colony-stimulating factor in patients with
malignant lymphoma
A Ohsaka, S Kitagawa, S Sakamoto, Y Miura, N Takanashi, F Takaku and M Saito
Department of Medicine, Jichi Medical School, Tochigi-ken, Japan.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was
administered (50 to 800 micrograms/m2) once daily as a half-hour
intravenous (IV) infusion for 14 days to seven patients with malignant
lymphoma. In all patients, administration of rhG-CSF not only ameliorated
the decrease in absolute neutrophil count after the cytotoxic chemotherapy
but also enhanced superoxide (O2-) release in neutrophils stimulated by
N-formyl-methionyl-leucyl-phenylalanine (FMLP). The priming effect of
rhG-CSF on neutrophil O2- release was rapid (evident within 6.5 hours) and
sustained at least for 24 hours after a single IV administration of
rhG-CSF. The responsiveness to further in vitro challenge of rhG-CSF was
lost or reduced in neutrophils isolated after rhG-CSF treatment, indicating
that neutrophils already primed in vivo by rhG-CSF are desensitized to this
factor. In contrast to the results obtained with FMLP, when phorbol
myristate acetate (PMA) was used as stimulus, no consistent enhancement of
O2- release was observed, suggesting that rhG-CSF modulates the signal
transduction pathways linked to FMLP receptors rather than increases the
components of the O2- producing enzyme complexes. Administration of rhG-CSF
also rapidly (evident within 15 minutes) caused an increase in expression
of neutrophil C3bi-receptors that was sustained for at least 24 hours after
a single IV administration of rhG- CSF. Pharmacokinetic study of rhG-CSF
showed a half-life (t1/2) of 114 min. These findings show that rhG-CSF is a
potent activator for neutrophil functions both in vivo and in vitro.
Volume 74,
Issue 8,
pp. 2743-2748,
12/01/1989
Copyright © 1989 by The American Society of Hematology
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