Evidence for the presence of CFU-E with increased in vitro sensitivity to erythropoietin in sickle cell anemia.
To investigate the cellular events that accompany erythroid hyperplasia, we studied several effects of erythropoietin (Epo) on marrow CFU-E in sickle cell anemia (SCA). We measured CFU-E number, CFU-E growth as a function both of Epo exposure time and of Epo concentration, and suppression of Epo-induced CFU-E formation by anti-Epo antiserum. With 0.5 U Epo/ml, the number of CFU-E was elevated in SCA (1,087 +/- 520) compared to normal (430 +/- 130). CFU-E were formed even when Epo was immediately neutralized by a 1/150 dilution of anti-Epo. After 40 hr of Epo exposure, only 2% of total CFU-E were expressed in normal marrow, whereas 12%-40% of CFU-E were expressed in SCA. Inhibition of CFU-E growth required at least 1/50 dilution of anti-Epo in SCA and a 1/300 dilution in normal marrow. In contrast to normal, a small number (5%-20%) of CFU-E were expressed in the absence of added Epo in SCA, and this pool required a 1/150 dilution of anti-Epo for inhibition. The Epo dose-response curve in SCA revealed a peak in colony formation around 0.1 U Epo/ml and 0.5 U Epo/ml, whereas only one peak at 0.5 U Epo/ml was seen in normals. These data strongly suggest that, in response to the demands of chronic erythroid hyperplasia in SCA, a pool of CFU-E is present characterized by increased in vitro sensitivity to Epo.
D000755:Anemia, Sickle Cell / Q000097:blood* / Q000473:pathology; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000097:blood / Q000276:immunology / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia / Q000097:blood / Q000473:pathology; D007106:Immune Sera / Q000494:pharmacology; D066298:In Vitro Techniques; D011817:Rabbits
D007106:Immune Sera; D004921:Erythropoietin