Stem Cell Migration Induced by Erythropoietin or Haemolytic Anaemia: the Effects of Actinomycin and Endotoxin Contamination of Erythropoietin Preparations

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Abstract
The injection of erythropoietin [EP] or the induction of anemia with phenylhydrazine leads to changes in murine pluripotent and granulocyte-macrophage stem cells indicating migration from marrow to spleen. To evaluate the interrelationship between erythroid differentiation and stem cell migration erythroid differentiation was selectively suppressed with actinomycin D. Anemia or EP injection resulted in stem cell changes consistent with migration. Actinomycin blocked these changes in anemic but not EP injected mice while blocking erythropoiesis in both groups. The EP contained from 0.01-1000 .mu.g/ml of endotoxin as defined by the Limulus test. It decreased marrow erythropoiesis and stimulated marrow granulopoiesis. Adsorption of the EP preparation with Limulus lysate removed endotoxin without decreasing EP activity. Adsorbed EP stimulated erythropoiesis and not granulopoiesis, and stem cell changes induced by its administration were largely blocked by actinomycin, suggesting that endotoxin in the non-adsorbed EP caused the actinomycin resistant stem cell changes. Actinomycin blocks erythroid differentiation and stem cell migration, suggesting that these 2 physiologic events are closely linked. The effects of injected EP on murine hemopoietic stem cells may, to a significant extent, be secondary to the presence of endotoxin in the EP preparations.
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