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Actions of human interleukin-4/B-cell stimulatory factor-1 on proliferation
and differentiation of enriched hematopoietic progenitor cells in culture
Y Sonoda, T Okuda, S Yokota, T Maekawa, Y Shizumi, H Nishigaki, S Misawa, H Fujii and T Abe
Department of Hygiene, Kyoto Prefectural University of Medicine, Japan.
We studied the effects of recombinant human interleukin-4 (IL-4) on colony
formation by enriched hematopoietic progenitors. IL-4 alone did not support
colony formation at all. When IL-4 was combined with granulocyte
colony-stimulating factor (G-CSF), the number of pure neutrophil colonies
increased three times over that supported by G-CSF alone. IL-4 added 5 days
after the addition of G-CSF failed to exert this synergistic effect,
indicating that IL-4 acts on the early stage of proliferation. The mapping
experiments (sequential observation of colony formation) have clearly shown
that IL-4 did not initiate progenitor cell proliferation. Based on these
data, IL-4 may possess a direct action on progenitor cells; however, it can
only act as a costimulant with G-CSF. In contrast, IL-4 had possible
inhibitory effects on macrophage colony formation supported by
interleukin-3 (IL- 3) and macrophage colony-stimulating factor (M-CSF). In
other words, IL- 4 may induce progenitor cells to become sensitive to G-CSF
and thereby induce neutrophil differentiation. Delayed addition experiments
demonstrated that human IL-4, unlike murine IL-4, could support neither
proliferation nor survival of erythroid burst or mixed colony forming
cells. Neutrophil colony forming cells only survived and recovered after
addition of G-CSF and erythropoietin on day 5 of incubation. On the other
hand, IL-3 supported neutrophil, erythroid burst, and mixed colony forming
cells as reported previously (Sonoda et al, Proc Natl Acad Sci USA,
85:4360, 1988). These results led us to propose that IL-4 possibly acts
with more mature progenitor cells than those of IL-3 or
granulocyte-macrophage (GM)-CSF.
Volume 75,
Issue 8,
pp. 1615-1621,
04/15/1990
Copyright © 1990 by The American Society of Hematology
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