Erythropoietin, an Autocrine Regulator? Serum-Free Production of Erythropoietin by Cloned Erythroid Cell Lines

Production of lymphoid and myeloid growth regulatory factors by hematopoietic cells is well documented. On the other hand, the major site of production of erythropoietin (Epo), which regulates physiologic red blood cell development, is thought to be the kidney. Here we report the isolation of multip...

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Bibliographic Details
Published in:Blood 1986-07, Vol.68 (1), p.263-268
Main Authors: Hankins, W. David, Schooley, John, Eastment, Christina
Format: Article
Language:English
Subjects:
Animal cells
Animals
Biological and medical sciences
Biotechnology
Blood
Cell Line
Cell metabolism, cell oxidation
Cell physiology
Chromatography, Gel
Clone Cells
Culture Media
Erythropoiesis
Erythropoietin - biosynthesis
Erythropoietin - physiology
Eukaryotic cell cultures
Friend murine leukemia virus
Fundamental and applied biological sciences. Psychology
Leukemia, Erythroblastic, Acute - metabolism
Leukemia, Experimental - metabolism
Methods. Procedures. Technologies
Mice
Miscellaneous
Molecular and cellular biology
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Summary:Production of lymphoid and myeloid growth regulatory factors by hematopoietic cells is well documented. On the other hand, the major site of production of erythropoietin (Epo), which regulates physiologic red blood cell development, is thought to be the kidney. Here we report the isolation of multiple erythroleukemia cell lines that produce erythropoietic factors and present extensive biological, immunologic, and biochemical evidence to document that the active agent is Epo. The erythropoietic activity was neutralized by Epo antiserum and exhibited physical properties indistinguishable from those of human and sheep Epo. Positive lines produced between 0.1 and 1.5 U/mL of Epo, which stimulated erythropoiesis in vivo and in vitro in nine biological assays. Twenty sublines derived from single cells were inducible for hemoglobin and spectrin synthesis. All the sublines produced Epo. Production of the hormone continued when the cells were seeded in the absence of serum. Our finding that multiple independent isolates produce Epo raises the possibility that Epo production by erythroid precursors may play a role in normal erythropoiesis or, alternatively, that Epo gene activation may be a relatively common occurrence that contributes to, or is associated with, certain forms of virus-induced leukemias. © 1986 by Grune & Stratton, Inc.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V68.1.263.263