title: Increased BPA production modulates Epo sensitivity of circulating BFU-E in sickle cell anemia.
abstract: 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.
authors.affiliation: Albert Einstein College of Medicine, Department of Medicine, Bronx, New York.
authors.forename: H
authors.initials: H
authors.lastname: Croizat
authors.forename: R L
authors.initials: RL
authors.lastname: Nagel
mesh_terms: 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
chemical_list: D004921:Erythropoietin; D008747:Methylcellulose