Nishimura Kazuhiko, Nakaya Haruna, Nakagawa Hiroshi, Matsuo Saburo, Ohnishi Yoshihiro, Yamasaki Shinji
Laboratory of Bioenvironmental Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.
J Parasitol. 2011 Feb;97(1):88-93. doi: 10.1645/GE-2522.1. Epub 2010 Sep 3.
Anemia generated from African trypanosome infection is considered an important symptom in humans and in domestic animals. In order to recover from anemia, the process of erythropoiesis is essential. Erythropoiesis is affected by erythropoietin (EPO), an erythropoietic hormone, supplying iron and inflammatory and proinflammatory cytokines. However, the role of these factors in erythropoiesis during African trypanosome infection remains unclear. In the present study, we analyze how erythropoiesis is altered in anemic Trypanosoma brucei brucei (interleukin-tat 1.4 strain [ILS])-infected rats. We report that the packed cell volume (PCV) of blood from ILS-infected rats was significantly lower 4 days after infection, whereas the number of reticulocytes, as an index of erythropoiesis, did not increase. The level of EPO mRNA in ILS-infected rats did not increase from the third day to the sixth day after infection, the same time that the PCV decreased. Kidney cells of uninfected rats cultured with ILS trypanosome strain for 8 hr in vitro decreased EPO mRNA levels. Treatment of both ILS and cobalt chloride mimicked hypoxia, which restrained the EPO-production-promoting effect of the cobalt. Messenger RNA levels of β-globin and transferrin receptor, as markers of erythropoiesis in the bone marrow, also decreased in ILS-infected rats. Levels of hepcidin mRNA, which controls the supply of iron to the marrow in liver, were increased in ILS-infected rats; however, the concentration of serum iron did not change. Furthermore, mRNA levels of interleukin-12, interferon-γ, tumor necrosis factor-α, and macrophage migration inhibitory factor in the spleen, factors that have the potential to restrain erythropoiesis in bone marrow, were elevated in the ILS-infected rats. These results suggest that ILS infection in rats affect erythropoiesis, which responds by decreasing EPO production and restraining its function in the bone marrow.
由非洲锥虫感染引起的贫血被认为是人类和家畜的一种重要症状。为了从贫血中恢复，红细胞生成过程至关重要。红细胞生成受促红细胞生成素（EPO）影响，EPO是一种促红细胞生成激素，还受铁以及炎性和促炎细胞因子的影响。然而，这些因素在非洲锥虫感染期间对红细胞生成的作用仍不清楚。在本研究中，我们分析了感染布氏布氏锥虫（白细胞介素- tat 1.4株[ILS]）的贫血大鼠的红细胞生成是如何改变的。我们报告称，感染ILS的大鼠在感染后4天血液的血细胞比容（PCV）显著降低，而作为红细胞生成指标的网织红细胞数量并未增加。感染ILS的大鼠中EPO mRNA水平在感染后第三天到第六天没有增加，而此时PCV下降。未感染的大鼠肾细胞在体外与ILS锥虫株培养8小时后EPO mRNA水平降低。ILS和氯化钴处理均模拟了缺氧状态，这抑制了钴对EPO生成的促进作用。作为骨髓中红细胞生成标志物的β-珠蛋白和转铁蛋白受体的mRNA水平在感染ILS的大鼠中也降低了。控制肝脏中铁向骨髓供应的铁调素mRNA水平在感染ILS的大鼠中升高；然而，血清铁浓度没有变化。此外，在感染ILS的大鼠中，脾脏中白细胞介素-12、干扰素-γ、肿瘤坏死因子-α和巨噬细胞迁移抑制因子的mRNA水平升高，这些因子有可能抑制骨髓中的红细胞生成。这些结果表明，大鼠感染ILS会影响红细胞生成，红细胞生成的反应是减少EPO生成并抑制其在骨髓中的功能。
