A mouse model of anemia of inflammation: complex pathogenesis with partial dependence on hepcidin
A mouse model of anemia of inflammation: complex pathogenesis with partial dependence on hepcidin
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DOI：
10.1182/blood-2013-08-521419
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发表时间：
2014-02-20
期刊：
影响因子：
20.3
通讯作者：
Ganz, Tomas
中科院分区：
文献类型：
--
作者：
Kim, Airie;Fung, Eileen;Ganz, Tomas
贫血是感染和炎症性疾病的常见并发症，但这种情况的少数小鼠模型尚未得到很好的表征。我们详细分析了注射热灭活的流产布鲁氏菌引起的贫血的发病机制，并通过比较野生型 (WT) 和缺铁 hepcidin-1 敲除 (Hamp-KO) 小鼠来检查铁调素的贡献。 B 流产治疗的 WT 小鼠出现严重贫血，血红蛋白在 14 天时降至最低点，并在 28 天时部分恢复。在炎症标志物和铁调素早期增加后，WT 小鼠表现出低铁血症，尽管肝脏中有铁积累。第 1 天至第 7 天期间，红细胞生成受到抑制，红细胞破坏增加，如血涂片上的裂红细胞和红细胞寿命缩短所证明的那样。 14 天后红细胞生成开始恢复，但铁限制。与WT小鼠相比，B abortus治疗的Hamp-KO小鼠贫血较轻，不受铁限制，并且恢复较快。与严重的人类炎症性贫血类似，B 型流产模型显示炎症性贫血的多因素发病机制，包括铁调素增加导致的铁限制、红细胞生成的短暂抑制和红细胞寿命缩短。消除铁调素可缓解铁限制并改善贫血。
Anemia is a common complication of infections and inflammatory diseases, but the few mouse models of this condition are not well characterized. We analyzed in detail the pathogenesis of anemia induced by an injection of heat-killed Brucella abortus and examined the contribution of hepcidin by comparing wild-type (WT) to iron-depleted hepcidin-1 knockout (Hamp-KO) mice. B abortus-treated WT mice developed severe anemia with a hemoglobin nadir at 14 days and partial recovery by 28 days. After an early increase in inflammatory markers and hepcidin, WT mice manifested hypoferremia, despite iron accumulation in the liver. Erythropoiesis was suppressed between days 1 and 7, and erythrocyte destruction was increased as evidenced by schistocytes on blood smears and shortened red blood cell lifespan. Erythropoietic recovery began after 14 days but was iron restricted. In B abortus-treated Hamp-KO compared with WT mice, anemia was milder, not iron restricted, and had a faster recovery. Similarly to severe human anemia of inflammation, the B abortus model shows multifactorial pathogenesis of inflammatory anemia including iron restriction from increased hepcidin, transient suppression of erythropoiesis, and shortened erythrocyte lifespan. Ablation of hepcidin relieves iron restriction and improves the anemia.