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Direct synergistic effects of leukemia inhibitory factor on hematopoietic
progenitor cell growth: comparison with other hematopoietins that use the
gp130 receptor subunit
JR Keller, JM Gooya and FW Ruscetti
Biological Carcinogenesis and Development Program, Science Applications
International Corporation Frederick, MD, USA.
Because leukemia inhibitory factor (LIF) has little or no effect on murine
hematopoietic progenitor cell growth yet enhances hematopoiesis in vivo, we
sought to determine whether the effects of LIF were directly or indirectly
mediated, or a combination of both. Although LIF alone or in combination
with granulocyte-macrophage colony-stimulating factor (GM-CSF) or
interleukin-3 (IL-3) has no effect on colony formation of unfractionated
bone marrow cells (BMCs), it enhances M-CSF- induced colony formation. In
comparison, LIF synergizes with IL-3, GM- CSF, M-CSF, and Steel Factor
(SLF) to promote the colony formation of partially purified
lineage-negative (Lin-) BM progenitors without altering their
differentiation. These effects were directly mediated since identical
results were observed in single-cell assays. Comparing the effect of LIF
with other members of this subclass of hematopoietins (IL-6, oncostatin M
[OSM], and ciliary neurotrophic factor [CNTF]), we found that while LIF and
IL-6 equally synergize with M-CSF and SLF to promote the colony formation
of Lin- BMCs, OSM, and CNTF have no effect. In agreement with OSMs ability
to directly bind gp130, preincubation of BMCs with OSM inhibits progenitor
cell growth stimulated by the combination of LIF or IL-6 plus SLF. LIF can
also directly enhance the growth of further purified more primitive Lin- c-
kit+ progenitor cells in the presence of IL-3, GM-CSF, or SLF. Thus, LIF
can directly synergize with growth factors to promote the proliferation of
purified hematopoietic progenitors, suggesting that the direct effects of
LIF on hematopoietic cell growth can, in part, explain the observed
hematopoietic effects in vivo. This is a US government work. There are no
restrictions on its use.
Volume 88,
Issue 3,
pp. 863-869,
08/01/1996
Copyright © 1996 by The American Society of Hematology
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