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Increased response of erythroid progenitors to interleukin‐3 in sickle cell anemia: CFU‐E‐like behavior of circulating erythroid progenitors in liquid culture
Author(s) -
Isoyama Keiichi,
Baliga Surendra,
Shah Arvind,
Mankad Vipul N.
Publication year - 1991
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.2830380206
Subject(s) - erythropoietin , progenitor cell , peripheral blood mononuclear cell , medicine , endocrinology , anemia , immunology , biology , erythropoiesis , interleukin 3 , andrology , t cell , stem cell , in vitro , immune system , interleukin 21 , biochemistry , microbiology and biotechnology
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 < 0.0001). At low doses of EPO, BFU‐E‐derived colonies were significantly increased in SCA patients compared with controls (each P < 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 < 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 < 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.