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Effects of recombinant human erythropoietin on megakaryocytes and on
platelet production in the rat
MV Berridge, JK Fraser, JM Carter and FK Lin
Institute of Medical Research, Wellington School of Medicine, New Zealand.
The contention that erythropoietin (Epo) affects platelet production was
investigated in the rat with recombinant human Epo (rHuEpo). In normal
rats, Epo caused a dose-dependent increase in both reticulocyte and
platelet numbers, the reticulocyte response preceding that of platelets.
Withdrawal of Epo resulted in reticulocytes and platelets returning to
control levels. [75Se]-selenomethionine incorporation into platelets was
also enhanced in response to Epo. Chronic daily administration of rHuEpo
resulted in steady state erythrocyte levels after 12 to 14 days, which were
elevated 20% above controls. Attainment of this steady state was associated
with both reticulocytes and platelets returning to control levels despite
continued administration of Epo, an effect not associated with a change in
the half-life of circulating Epo. In polycythemic rats a platelet response
was observed before an effect on reticulocytes. Erythropoietin caused a
2.4-fold increase in the frequency of small acetylcholinesterase-positive
cells within 24 hours, and increased the mean megakaryocyte diameter within
48 hours. Furthermore, the [3H]-thymidine labeling index of megakaryocytes
from rats treated for 24 hours with rHuEpo was increased for all stages of
megakaryocyte maturation. These results support the proposal of an effect
of Epo on rat megakaryocytes causing increased platelet production.
Volume 72,
Issue 3,
pp. 970-977,
09/01/1988
Copyright © 1988 by The American Society of Hematology
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