Inappropriately low reticulocytosis in severe malarial anemia correlates with suppression in the development of late erythroid precursors
Inappropriately low reticulocytosis in severe malarial anemia correlates with suppression in the development of late erythroid precursors
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DOI：
10.1182/blood-2003-08-2887
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发表时间：
2004-05-15
期刊：
影响因子：
20.3
通讯作者：
Stevenson, MM
中科院分区：
文献类型：
--
作者：
Chang, KH;Tam, MF;Stevenson, MM
网织红细胞过多症可能会加重疟疾性贫血，但其潜在机制尚不清楚。在这项研究中，幼稚和感染的小鼠用重组鼠促红细胞生成素（EPO），红细胞生成的上游事件受血液阶段的夏氏疟原虫AS进行了调查。与EPO治疗的小鼠相比，无论是否接受EPO治疗，疟疾感染均导致TER119（+）成红细胞的次优增加。此外，感染小鼠中较低比例的TER 119（+）成红细胞正在经历终末分化，成为成熟的产生血红蛋白的成红细胞。感染期间成红细胞成熟受损与转铁蛋白受体（CD71）表达从TER119（+）群体向B220（+）群体的转变有关。此外，在感染过程中TER119（+）成红细胞的次优增加与体外脾细胞对EPO刺激的钝增殖反应相一致，尽管这些脾细胞高频率表达EPO受体（EPOR）。综上所述，这些数据表明，在疟疾期间，EPO诱导的早期EPOR阳性红系祖细胞的增殖受到抑制，这可能导致TIER119（+）成红细胞的次优生成。CD71表达的变化可能导致这些成红细胞的终末成熟受损。因此，疟疾期间网织红细胞缺乏与红系前体细胞增殖、分化和成熟受到抑制有关。(C)2004年，美国血液学会。
Inappropriately low reticulocytosis may exacerbate malarial anemia, but the underlying mechanism is not clear. In this study, naive and infected mice were treated with recombinant murine erythropoietin (EPO), and the upstream events of erythropoiesis affected by blood-stage Plasmodium chabaudi AS were investigated. Malaria infection, with or without EPO treatment, led to a suboptimal increase in TER119(+) erythroblasts compared with EPO-treated naive mice. Furthermore, a lower percentage of TER119(+) erythroblasts in infected mice were undergoing terminal differentiation to become mature hemoglobin-producing erythroblasts. The impaired maturation of erythroblasts during infection was associated with a shift in the transferrin receptor (CD71) expression from the TER119(+) population to B220(+) population. Moreover, the suboptimal increase in TER119(+) erythroblasts during infection coincided with a blunted proliferative response by splenocytes to EPO stimulation in vitro, although a high frequency of these splenocytes expressed EPO receptor (EPOR). Taken together, these data suggest that during malaria, EPO-induced proliferation of early EPOR-positive erythroid progenitors is suppressed, which may lead to a suboptimal generation of TIER119(+) erythroblasts. The shift in CD71 expression may result in impaired terminal maturation of these erythroblasts. Thus, inadequate reticulocytosis during malaria is associated with suppressed proliferation, differentiation, and maturation of erythroid precursors. (C) 2004 by The American Society of Hematology.