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Stage-specific expression of c-kit protein by murine hematopoietic
progenitors
N Katayama, JP Shih, S Nishikawa, T Kina, SC Clark and M Ogawa
Department of Medicine, Medical University of South Carolina.
We have analyzed c-kit expression by hematopoietic progenitors from normal
and 5-fluorouracil (5-FU)-treated mice by staining with monoclonal
anti-c-kit antibody ACK-4. Marrow cells that were enriched for progenitors
by a combination of metrizamide density separation and negative
immunomagnetic selection with lineage-specific monoclonal antibodies
(MoAbs) were separated into three populations based on the level of c-kit
expression, c-kit(high), c-kit(low), and c-kit-. The majority of
colony-forming cells from normal mice were in c-kit(high) population,
whereas most of the progenitors from 5-FU-treated mice were in the
c-kit(low) population. Optimal colony formation from c-kit(low) cells from
5-FU-treated mice required the interactions of at least two factors among
interleukin-3 (IL-3), IL-11 and steel factor (SF) whereas colony formation
from c-kit(high) cells of normal mice was supported well by IL-3 alone.
Blast cells that were derived from 5-day culture of c-kit(low) post 5-FU
cells were c-kit(high). These observations suggest that the primitive
hematopoietic progenitors in cell cycle dormancy are c-kit(low) whereas
actively cell cycling maturer progenitors are c- kit(high). Mature cells,
with the exception of mast cells, derived from secondary culture of the
c-kit(high) blast cells expressed little, if any, c-kit. These results are
consistent with a model in which c-kit expression progresses from low
levels on primitive, dormant multipotent progenitors to high levels on
later, actively cycling progenitors, and finally, decreases to very low or
undetectable levels on most mature blood cells, with the exception of mast
cells.
Volume 82,
Issue 8,
pp. 2353-2360,
10/15/1993
Copyright © 1993 by The American Society of Hematology
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