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Human Hematopoietic Progenitors Express Erythropoietin
T. Stopka,
J.H. Zivny,
P. Stopkova,
J.F. Prchal, and
J.T. Prchal
From the Department of Medicine, University of Alabama at Birmingham,
Birmingham, AL and the Division of Hematology/Oncology, McGill
University, Montreal, Canada.
Erythropoietin (EPO) is a factor essential for erythroid cell
proliferation, differentiation, and survival. The production of EPO by
the kidneys in response to hypoxia and anemia is well documented. To
determine whether EPO is also produced by hematopoietic cells, we
analyzed the expression of EPO in normal human hematopoietic progenitors and in their progeny. Undifferentiated
CD34+lin hematopoietic progenitors do not
have detectable EPO mRNA. Differentiating CD34+ cells
that are stimulated with recombinant human EPO in serum-free liquid
cultures express both EPO and EPO receptor (EPOR). Because CD34+ cells represent a heterogeneous cell population, we
analyzed individual burst-forming units-erythroid (BFU-E) and
nonerythroid colony-forming unit-granulocyte-macrophage colonies for
EPO mRNA. Only BFU-E colonies were positive for EPO mRNA. Lysates from
pooled BFU-E colonies stained positively for EPO by immunoblotting. To further confirm the intrinsic nature of erythroid EPO, we replaced extrinsic EPO in erythroid colony cultures with EPO-mimicking peptide
(EMP). We show EPO expression in the EMP-stimulated BFU-Es at both mRNA
and protein levels. Stimulation of bone marrow mononuclear cells
(BMMCs) with EMP upregulated EPO expression. Furthermore, we found EPO
and EPOR mRNAs as well as EPO protein in K562 cells, a human
erythroleukemia cell line. Stimulation of K562 cells with EMP
upregulated EPO expression. We suggest that EPO of erythroid origin may
have a role in the regulation of erythropoiesis.
Blood, Vol. 91 No. 10 (May 15), 1998:
pp. 3766-3772
© 1998 by The American Society of Hematology.
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