Modulation of the course and outcome of blood-stage malaria by erythropoietin-induced reticulocytosis
Modulation of the course and outcome of blood-stage malaria by erythropoietin-induced reticulocytosis
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DOI：
10.1086/381458
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发表时间：
2004-02-15
影响因子：
6.4
通讯作者：
Stevenson, MM
中科院分区：
文献类型：
--
作者：
Chang, KH;Tam, M;Stevenson, MM
严重贫血是疟疾的一个主要危及生命的并发症。研究了红细胞生成素（Epo）和红细胞生成在血期疟疾中的作用。通过用多克隆抗人促红细胞生成素中和抗体治疗chabaudi疟原虫感染的C57BL/6 （B6）抗疟疾小鼠，我们证实了促红细胞生成素诱导的网状细胞吞噬对缓解疟疾贫血和促进宿主存活具有重要作用。通过使用外源性重组小鼠Epo诱导疟疾易感小鼠A/J和B6小鼠在感染期间的不同时期的红细胞生成，发现网织红细胞缺血症的过早发作可增加寄生虫的繁殖并导致致命感染。然而，用促红细胞生成素治疗及时诱导网织红细胞增多症可减轻疟疾贫血，提高生存率。我们的数据揭示了epo诱导的网状红细胞增多症在调节血期疟疾的过程和结果中的重要作用。然而，与不及时使用促生成素治疗相关的死亡率增加的机制以及与及时使用促生成素治疗相关的保护作用增加的机制仍有待研究。
Severe anemia is a major life-threatening complication of malaria. The roles of erythropoietin (Epo) and erythropoiesis during blood-stage malaria were investigated. By treating Plasmodium chabaudi AS-infected C57BL/6 (B6) mice, which are resistant to malaria, with polyclonal anti-human Epo neutralizing antibody, we demonstrated that Epo-induced reticulocytosis was important for alleviating malarial anemia and for host survival. By inducing erythropoiesis in A/J mice, which are susceptible to malaria, and in B6 mice at various periods during infection, by use of exogenous recombinant murine Epo, untimely onset of reticulocytosis was shown to augment multiplication of parasites and result in lethal infection. However, timely inducement of reticulocytosis with Epo treatment alleviated malarial anemia and increased survival. Our data reveal the important role of Epo-induced reticulocytosis in modulating the course and outcome of blood-stage malaria. However, the mechanisms underlying the increased mortality associated with untimely treatment with Epo and the increased protection associated with timely treatment with Epo remain to be investigated.