title: Increased response of erythroid progenitors to interleukin-3 in sickle cell anemia: CFU-E-like behavior of circulating erythroid progenitors in liquid culture.
abstract: Erythroid progenitors circulating in peripheral blood and their response to erythropoietin (EPO), interleukin-3 (IL3), and phytohemagglutinin-stimulated, lymphocyte-conditioned medium (PHALCM) were assessed in sickle cell anemia (SCA) patients and controls. SCA patients have significantly higher numbers of circulating burst-forming unit-erythroid (BFU-E) compared with controls (mean +/- SEM, 940.27 +/- 129.11 per ml and 86.56 +/- 19.74 per ml, respectively; P less than 0.0001). At low doses of EPO, BFU-E-derived colonies were significantly increased in SCA patients compared with controls (each P less than 0.05). The EPO dose required to produce 50% of maximum colony numbers was 47 times greater in control subjects than in SCA patients. Moreover, in 11 of 17 patients with SCA, spontaneous BFU-E-derived colonies were formed without added erythropoietin. This phenomenon was not observed in control subjects (P = 0.035). PHALCM developed from mononuclear cells of SCA patients had significantly greater stimulatory effect than did that derived from controls regardless of the source of target cells (each P less than 0.05). A two-step study of IL3 sensitivity of erythroid progenitors was conducted. First, in a liquid culture system, circulating erythroid progenitors of SCA patients and controls were incubated in the presence of varying doses of IL3. During a second step, CFU-E-like colonies were observed in methylcellulose cultures of these cells. The mean numbers of colony-forming unit-erythroid (CFU-E)-like colonies was significantly higher in SCA patients compared with control subjects at low doses of IL3 (each P less than 0.02). The increased response of erythroid progenitors to IL3 and the increased production of hemopoietic growth factors (IL3 or non-IL3) contribute to the hemopoietic response in SCA patients. These mechanisms and increased sensitivity of the BFU-E to EPO may explain lower than expected EPO levels in SCA patients.
authors.affiliation: Department of Pediatrics, University of South Alabama College of Medicine, Mobile.
authors.forename: K
authors.initials: K
authors.lastname: Isoyama
authors.forename: S
authors.initials: S
authors.lastname: Baliga
authors.forename: A
authors.initials: A
authors.lastname: Shah
authors.forename: V N
authors.initials: VN
authors.lastname: Mankad
mesh_terms: D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000502:physiology
chemical_list: D003470:Culture Media; D007377:Interleukin-3; D004921:Erythropoietin