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Synergistic effect of FLT-3 ligand on the granulocyte colony- stimulating
factor-induced mobilization of hematopoietic stem cells and progenitor
cells into blood in mice
Y Sudo, C Shimazaki, E Ashihara, T Kikuta, H Hirai, T Sumikuma, N Yamagata, H Goto, T Inaba, N Fujita and M Nakagawa
Second Department of Medicine, Kyoto Prefectural University of Medicine,
Kamigyoku, Japan.
We have previously shown that FLT-3 ligand (FL) mobilizes murine
hematopoietic primitive and committed progenitor cells into blood dose-
dependently. Whether FL also acts synergistically with granulocyte
colony-stimulating factor (G-CSF) to induce such mobilization has now been
investigated. Five- to 6-week-old C57BL/6J mice were injected
subcutaneously with recombinant human G-CSF (250 microg/kg), Chinese
hamster ovarian cell-derived FL (20 microg/kg), or both cytokines daily for
5 days. The number of colony-forming cells (CFCs) in peripheral blood
increased approximately 2-, 21-, or 480-fold after administration of FL,
G-CSF, or the two cytokines together, respectively, for 5 days. The number
of CFCs in bone marrow decreased after 3 days but was increased
approximately twofold after 5 days of treatment with G-CSF. The number of
CFCs in the bone marrow of mice treated with both FL and G-CSF showed a
3.4-fold increase after 3 days and subsequently decreased to below control
values. The number of CFCs in spleen was increased 24.2- and 93.7-fold
after 5 days of treatment with G-CSF alone or in combination with FL,
respectively. The number of colony- forming unit-spleen (CFU-S) (day 12) in
peripheral blood was increased 13.2-fold by G-CSF alone and 182-fold by
G-CSF and FL used together after 5 days of treatment. Finally, the number
of preCFU-S mobilized into peripheral blood was also increased by the
administration of FL and G-CSF. These observations show that FL
synergistically enhances the G-CSF-induced mobilization of hematopoietic
stem cells and progenitor cells into blood in mice, and that this
combination of growth factors may prove useful for obtaining such cells in
humans for transplantation.
Volume 89,
Issue 9,
pp. 3186-3191,
05/01/1997
Copyright © 1997 by The American Society of Hematology
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