Frazer David M, Wilkins Sarah J, Mirciov Cornel S G, Dunn Linda A, Anderson Gregory J
Iron Metabolism Laboratory, QIMR Berghofer Medical Research Institute, Herston, Australia.
Schools of Medicine, The University of Queensland, St Lucia, Australia.
Br J Haematol. 2016 Oct;175(2):308-317. doi: 10.1111/bjh.14206. Epub 2016 Jul 13.
In conditions such as β-thalassaemia, stimulated erythropoiesis can reduce the expression of the iron regulatory hormone hepcidin, increasing both macrophage iron release and intestinal iron absorption and leading to iron loading. However, in certain conditions, sustained elevation of erythropoiesis can occur without an increase in body iron load. To investigate this in more detail, we made use of a novel mouse strain (RBC14), which exhibits mild β-thalassaemia intermedia with minimal iron loading. We compared iron homeostasis in RBC14 mice to that of Hbb mice, a more severe model of β-thalassaemia intermedia. Both mouse strains showed a decrease in plasma iron half-life, although the changes were less severe in RBC14 mice. Despite this, intestinal ferroportin and serum hepcidin levels were unaltered in RBC14 mice. In contrast, Hbb mice exhibited reduced serum hepcidin and increased intestinal ferroportin. However, splenic ferroportin levels were increased in both mouse strains. These data suggest that in low-grade chronic haemolytic anaemia, such as that seen in RBC14 mice, the increased erythroid iron requirements can be met through enhanced macrophage iron release without the need to increase iron absorption, implying that hepcidin is not the sole regulator of macrophage iron release in vivo.
在β地中海贫血等病症中，受刺激的红细胞生成可降低铁调节激素铁调素的表达，增加巨噬细胞铁释放和肠道铁吸收，从而导致铁过载。然而，在某些情况下，红细胞生成持续升高时，机体铁负荷却不会增加。为了更详细地研究这一现象，我们利用了一种新型小鼠品系（RBC14），它表现出轻度中间型β地中海贫血且铁负荷最小。我们将RBC14小鼠的铁稳态与Hbb小鼠（一种更严重的中间型β地中海贫血模型）的铁稳态进行了比较。两种小鼠品系的血浆铁半衰期均缩短，不过RBC14小鼠的变化没那么严重。尽管如此，RBC14小鼠的肠道铁转运蛋白和血清铁调素水平并未改变。相比之下，Hbb小鼠的血清铁调素降低，肠道铁转运蛋白增加。然而，两种小鼠品系的脾脏铁转运蛋白水平均升高。这些数据表明，在轻度慢性溶血性贫血中，如在RBC14小鼠中所见，红细胞对铁需求的增加可通过增强巨噬细胞铁释放来满足，而无需增加铁吸收，这意味着铁调素并非体内巨噬细胞铁释放的唯一调节因子。
