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Roles of erythropoietin, insulin-like growth factor 1, and unidentified
serum factors in promoting maturation of purified murine erythroid
colony-forming units
SH Boyer, TR Bishop, OC Rogers, AN Noyes, LP Frelin and S Hobbs
Department of Medicine, Johns Hopkins University School of Medicine,
Baltimore, MD 21205.
We have used 75% to 90% pure murine erythroid colony-forming units (CFU- E)
to delineate the processes and factors underlying their maturation. These
CFU-E form 32 cell colonies and are drawn from what we term generation I of
a six-generation long maturation sequence (Landschulz et al, Blood 79:2749,
1992). Applying assays of 59Fe-heme biosynthesis and colony numbers as
measures of maturation and analyses of DNA degradation as an index of
programmed cell death, we find that (1) erythropoietin (Epo) enhances
maturation throughout most of its course; (2) Epo first seems able to
forestall DNA degradation when CFU-E reach generation II; (3) the processes
that Epo elicits thereafter start to persist when Epo is withdrawn; (4)
insulin-like growth factor I (IGF-I) also forestalls DNA breakdown, but
later loses effectiveness; (5) IGF-I adds little to maturation when Epo
levels are high, but when Epo levels are low, enhances it substantially;
and (6) for maturation to be entirely optimal, an unidentified serum
factor(s) is probably required when Epo levels are high and is certainly
needed when Epo levels are like those in normal animals. Quantitatively,
about 40% of optimal in vitro erythropoiesis at normal Epo levels depends
on Epo alone, another 30% or less on the addition of IGF-I, and the
remaining 30% or more on the addition of unidentified serum factor(s).
Applied together, these three or more factors lead to two-thirds of the
maximum maturation realized with saturating Epo levels. Because we also
find that heme accumulated in CFU-E culture can closely approach levels in
red blood cells, we suppose that our conclusions apply as well to CFU-E
maturation in vivo.
Volume 80,
Issue 10,
pp. 2503-2512,
11/15/1992
Copyright © 1992 by The American Society of Hematology
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