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首页> 外文会议>International symposium on halogenated persistent organic pollutants >EXACERBATED HEMOLYTIC ANEMIA WITH EXPOSURE TO PHENYLHYDRAZINE IN HRI DEFICIENCY
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EXACERBATED HEMOLYTIC ANEMIA WITH EXPOSURE TO PHENYLHYDRAZINE IN HRI DEFICIENCY

机译：在HRI缺乏时暴露于苯并肼的急性溶血性贫血

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摘要

Phenylhydrazine (PHZ) exposure may cause adverse health issues via inhalation, ingestion, or dermal or eye contact. PHZ has been documented to cause severe hemolytic anemia, degenerative lesions in livers and kidneys and lung tumors in animals or humans. Heme-regulated eIF2α kinase (HRI) plays an essential protective role in anemias of iron deficiency, erythroid protoporphyria, and β-thalassemia. The current study indicates that HRI is important for macrophage maturation, although it is expressed at a lower level in macrophages. In HRI deficiency, macrophages do not develop the typical morphology and expressed less CSF-1R protein. Consequently, expression levels of macrophage cell-surface markers F4/80 and CD11b and the core component of the receptor complex for LPS, TLR4, are reduced in Hri–/– compared with Hri+/+ macrophages. This is the first demonstration that HRI protein is expressed and functional in nonerythroid cell types. Further, an impairment of erythrophagocytosis by Hri–/– macrophages was observed under chronic hemolytic anemia induced by PHZ in vivo, providing evidence for the role of HRI in recycling iron from senescent red blood cells. This work demonstrates that HRI deficiency attenuates iron homeostasis in mice, indicating a protective role for HRI in hemolytic anemia of inflammation with exposure to PHZ.
机译：苯肼（PHZ）暴露可能通过吸入，食入或皮肤或眼睛接触而引起不良健康问题。据报道，PHZ会引起严重的溶血性贫血，肝脏和肾脏的退行性病变以及动物或人类的肺部肿瘤。血红素调节的eIF2α激酶（HRI）在缺铁性贫血，类红细胞原卟啉症和β地中海贫血中起重要的保护作用。目前的研究表明HRI对于巨噬细胞成熟很重要，尽管它在巨噬细胞中的表达水平较低。在HRI缺乏的情况下，巨噬细胞不会形成典型的形态，并且表达的CSF-1R蛋白更少。因此，与Hri + / +巨噬细胞相比，Hri-/-降低了巨噬细胞表面标记F4 / 80和CD11b的表达水平以及LPS受体复合物的核心成分TLR4。这是HRI蛋白在非红系细胞类型中表达并起作用的第一个证明。此外，在体内由PHZ引起的慢性溶血性贫血下，观察到Hri-/-巨噬细胞对红细胞吞噬功能的损害，这为HRI在从衰老的红细胞回收铁中的作用提供了证据。这项工作证明HRI缺乏会减弱小鼠体内的铁稳态，表明HRI在暴露于PHZ的溶血性贫血性炎症中具有保护作用。

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  • 会议地点 Beijing(CN)
  • 作者

    Sijin Liu; Rajasekhar N.V.S.Suragani; Jane-Jane Chen;

  • 作者单位

    Research Center for Eco-Environmental Sciences,Chinese Academy of Sciences,Beijing 100085,China Harvard-MIT Division of Health Sciences and Technology,Massachusetts Institute of Technology,Cambridge,Massachusetts,USA;

    Harvard-MIT Division of Health Sciences and Technology,Massachusetts Institute of Technology,Cambridge,Massachusetts,USA;

    Harvard-MIT Division of Health Sciences and Technology,Massachusetts Institute of Technology,Cambridge,Massachusetts,USA;

  • 会议组织
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 环境分析化学;
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