Increased BPA production modulates Epo sensitivity of circulating BFU-E in sickle cell anemia.
We have examined the possibility that permanent "stress" hemopoiesis in sickle cell anemia (SS) patients leads to the modification of the behavior of circulating 14 day erythroid progenitor cells (BFU-E). In these patients we find that peripheral blood BFU-E are increased in number and have high sensitivity to erythropoietin (Epo). Maximal number of BFU-E are generated from peripheral blood of SS patients at 0.3-0.75 Epo/ml of culture compared to 1.5-2.0 U Epo/ml of culture in normals. Peripheral blood adherent cells depletion leads to the shift of Epo dose response curve, so that the Epo sensitivity of BFU-E significantly decreases. This result suggests that apparent Epo hypersensitivity reflects, in fact, an increased production of a burst promoting activity (BPA) by SS peripheral blood light density adherent (PB-LDA) cells. Experiments with conditioned medium by SS PB-LDA cells confirmed this interpretation. When peripheral blood light density non-adherent (PB-LDNA) cells of SS patients or normal individuals were plated in the presence of various concentrations of SS PB-LD cells conditioned medium and constant amounts of Epo, a dose dependent increase of the number of BFU-E was observed. When the same target cells were plated in the presence of PB-LD cells conditioned medium from normal individuals, such effect does not occur. We conclude that increased BPA production may play a role in the erythropoietic regulation during constant hemopoietic stress in sickle cell anemia and might partially explain the lower than expected Epo levels in these patients.
Croizat
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Albert Einstein College of Medicine, Department of Medicine, Bronx, New York.
Nagel
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D000755:Anemia, Sickle Cell / Q000503:physiopathology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004920:Erythropoiesis; D004921:Erythropoietin / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D008747:Methylcellulose
D004921:Erythropoietin; D008747:Methylcellulose