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Splenic primitive hematopoietic stem cell (PHSC) activity is enhanced by
steel factor because of PHSC proliferation
DE Harrison, KM Zsebo and CM Astle
Jackson Laboratory, Bar Harbor, ME 04609-0800.
To test whether primitive hematopoietic stem cells (PHSCs) are stimulated
by Steel (SI) factor (c-kit ligand) in vivo, donor mice were studied after
three or seven daily injections of SI factor. PHSC activity was measured as
long-term erythroid and lymphoid competitive repopulating ability. Cells to
be tested (usually marrow or spleen cells from treated donors) were mixed
with untreated competitor marrow that produces erythrocytes and lymphocytes
that are genetically distinguishable from the donors by differences in
hemoglobin (Hb) and glucosephosphate isomerase (GPI) markers. These cell
mixtures were injected into lethally irradiated hosts, and after 111 to 293
days, functional abilities of donor PHSC populations were assessed and
expressed as percentages of donor-type Hb and GPI in the host's circulating
erythrocytes and lymphocytes, respectively. A striking increase in splenic
PHSC activity occurred after seven daily injections of SI factor, with a
much smaller increase after three daily injections. Both three and seven
daily injections of SI factor slightly reduced marrow PHSC activity. Rapid
cycling greatly increases PHSC vulnerability to 5-fluorouracil (5FU). To
test whether SI factor stimulates PHSCs into rapid cycling, donor mice were
given a dose of 5FU in addition to SI factor. The increase in splenic PHSCs
after 7 days of treatment with SI factor occurred to a similar degree
whether donors were or were not treated with 5FU on day 8. However, a dose
of 5FU on day 4 of the SI factor treatments almost totally prevented the
increase in splenic PHSC activity. Apparently this increased activity
requires PHSC cycling throughout the period of SI factor treatment.
Volume 83,
Issue 11,
pp. 3146-3151,
06/01/1994
Copyright © 1994 by The American Society of Hematology
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