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Myeloid cell kinetics in mice treated with recombinant interleukin-3,
granulocyte colony-stimulating factor (CSF), or granulocyte-macrophage CSF
in vivo
BI Lord, G Molineux, Z Pojda, LM Souza, JJ Mermod and TM Dexter
Cancer Research Campaign Department of Experimental Haematology, Paterson
Institute for Cancer Research, Christie Hospital and Holt Radium Institute,
Manchester, UK.
Myeloid cell kinetics in mice treated with pure hematopoietic growth
factors have been investigated using tritiated thymidine labeling and
autoradiography. Mice were injected subcutaneously with 125 micrograms/kg
granulocyte colony-stimulating factor (G-CSF) (in some cases 5
micrograms/kg), or 10 micrograms/kg of granulocyte-macrophage CSF (GM-CSF),
or interleukin-3 (IL-3) every 12 hours for 84 hours. 3HTdR labeling was
performed in vivo after 3 days of treatment. G-CSF increased the peripheral
neutrophil count 14-fold and increased the proportion and proliferation
rate of neutrophilic cells in the marrow, suppressing erythropoiesis at the
same time. Newly produced mature cells were released into the circulation
within 24 hours of labeling, compared with a normal appearance time of
about 96 hours. By contrast, GM-CSF and IL-3 had little effect on either
marrow cell kinetics or on the rate of release of mature cells, although
GM-CSF did stimulate a 50% increase in peripheral neutrophils. Monocyte
production was also increased about eightfold by G-CSF and 1.5-fold by
GM-CSF, but their peak release was only slightly accelerated. While the
peripheral half- lives of the neutrophilic granulocytes were normal, those
of the monocytes were dramatically reduced, perhaps due to sequestration in
the tissues for functional purposes. The stimulated monocyte production in
the case of G-CSF required an additional five cell cycles, a level that
might have repercussions on the progenitor compartments.
Volume 77,
Issue 10,
pp. 2154-2159,
05/15/1991
Copyright © 1991 by The American Society of Hematology
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