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Interleukin-1 alpha enhances the in vitro survival of purified murine
granulocyte-macrophage progenitor cells in the absence of colony-
stimulating factors
DE Williams and HE Broxmeyer
Department of Medicine (Hematology/Oncology), Walther Medical Research
Institute, Indiana University School of Medicine, Indianapolis.
Interleukin-1 (IL-1), recently identified as hemopoietin-1, affects
hematopoiesis by presumably direct and indirect mechanisms. IL-1 stimulates
primitive hematopoietic stem cells to express receptors for the
granulocyte-macrophage colony-stimulating factors (GM-CSFs) and stimulates
CSF release from accessory cells. We used highly purified murine
granulocyte-macrophage progenitor cells (CFU-GM, up to 92% cloning
efficiency) to assess the effects of IL-1 alpha on the proliferation,
differentiation, and survival of these cells. The results demonstrated that
IL-1 alpha does not directly influence the proliferation or differentiation
of purified CFU-GM in the presence of plateau concentrations of purified
natural or recombinant CSFs, and IL- 1 alpha lacks intrinsic CSF activity
of its own. CSF deprivation studies showed that IL-1 alpha rapidly (within
one hour) promoted CFU- GM survival in the absence of CSF. This enhanced
survival stimulated by IL-1 alpha was observed with CFU-GM responding to
purified recombinant GM-CSF, natural M-CSF, recombinant G-CSF, recombinant
IL-3, or IL-3 in WEHI-conditioned medium, and no effect on the pattern of
CFU-GM differentiation occurred in cultures incubated with IL-1 alpha in
the absence of CSF. The IL-1 alpha effects on CFU-GM are probably due to a
direct action on progenitor cells because the presence or absence of
accessory cells did not alter the results and concentrations of the CSFs
that were too low to stimulate the proliferation of CFU-GM could not mimic
the IL-1 alpha effect on CFU-GM survival.
Volume 72,
Issue 5,
pp. 1608-1615,
11/01/1988
Copyright © 1988 by The American Society of Hematology
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