Haptoglobin reduces lung injury associated with exposure to blood.

Haptoglobin reduces lung injury associated with exposure to blood.
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DOI:
10.1152/ajplung.00115.2002
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发表时间:
2003-02
期刊:
American journal of physiology. Lung cellular and molecular physiology
影响因子:
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通讯作者:
Funmei Yang;D. Haile;F. Berger;D. Herbert;Emily Van Beveren;A. Ghio
Funmei Yang;D. Haile;F. Berger;D. Herbert;Emily Van Beveren;A. Ghio
中科院分区:
其他
文献类型:
--
作者:
Funmei Yang;D. Haile;F. Berger;D. Herbert;Emily Van Beveren;A. Ghio

文献摘要

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急性期蛋白触珠蛋白(Hp)的生物学功能可能与其结合血红蛋白(Hb)或调节免疫反应的能力有关。Hp在肺细胞中高水平表达,但其在肺中的保护作用尚不清楚。通过在肺泡巨噬细胞中过表达Hp的转基因小鼠,我们证明Hp可以减轻全血肺暴露时hb诱导的肺损伤。在转基因小鼠肺中,与野生型小鼠相比,Hb被更有效地去除,应激反应血红素加氧酶-1基因的诱导显著降低。在血液处理后24 h,转基因小鼠肺泡巨噬细胞中作为细胞内铁含量指标的铁蛋白水平也低于野生型小鼠。我们提出在肺泡巨噬细胞中存在hp介导的Hb分解代谢过程。这一过程可能与铁动员途径耦合,可能是减少溶血相关氧化损伤的有效机制。
The biological functions of the acute- phase protein haptoglobin (Hp) may be related to its ability to bind hemoglobin (Hb) or to modulate immune response. Hp is expressed at a high level in lung cells, yet its protective role(s) in the lung is not known. With the use of transgenic mice overexpressing Hp in alveolar macrophages, we demonstrated that Hp diminished Hb-induced lung injury when the lung was exposed to whole blood. In transgenic mouse lungs, Hb was more efficiently removed, and the induction of stress- responsive heme oxygenase-1 gene was significantly lower when compared with wild-type mice. At 24 h after blood treatment, the ferritin level that serves as an index for intracellular iron content was also lower in alveolar macrophages in transgenic mice than in wild-type mice. We propose that an Hp-mediated Hb catabolism process exists in alveolar macrophages. This process is likely coupled to an iron mobilization pathway and may be an efficient mechanism to reduce oxidative damage associated with hemolysis.