Hemopexin in severe inflammation and infection: mouse models and human diseases.
Hemopexin in severe inflammation and infection: mouse models and human diseases.
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DOI：
10.1186/s13054-015-0885-x
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发表时间：
2015-04-15
期刊：
影响因子：
--
通讯作者：
Warren HS
中科院分区：
文献类型：
--
作者：
Lin T;Maita D;Thundivalappil SR;Riley FE;Hambsch J;Van Marter LJ;Christou HA;Berra L;Fagan S;Christiani DC;Warren HS
无细胞血浆血红蛋白与脓毒症患者预后不良相关。在微生物TLR配体和/或内源性介质存在的情况下，细胞外血红蛋白和次生释放血红素会放大炎症。Hemopexin是一种血浆蛋白，可以与血红素结合，具有非凡的亲和力，可以阻断这些作用，并被提议作为一种可能的治疗方法来减少危重患者的炎症。我们研究了内毒素血症、烧伤感染和腹膜炎的小鼠模型，以评估血红素的补充策略是否合理。我们还测量了三种患者群体的少量血凝素，这些患者群体可能是血凝素治疗的逻辑群体：败血症和ARDS患者，严重烧伤患者和早产儿。尽管疾病严重，但在每个小鼠模型中，平均血浆血凝素水平高于基线。然而，在三个患者群体中，许多患者的血浆血凝素水平下降或明显下降。当利用小鼠模型来代表血红素发挥作用的急性人类炎症性疾病时，血红素在小鼠和人类中的潜在不同行为可能是重要的考虑因素。研究结果提出了一种可能性，即在一些急性呼吸窘迫综合征（ARDS）患者、烧伤患者或早产儿中，血红素的减少可能导致血红素的中和或清除不足，这些患者可能从血红素治疗中获益。本文的在线版本（doi:10.1186/s13054-015-0885-x）包含补充材料，可供授权用户使用。
Cell-free plasma hemoglobin is associated with poor outcome in patients with sepsis. Extracellular hemoglobin and secondarily released heme amplify inflammation in the presence of microbial TLR ligands and/or endogenous mediators. Hemopexin, a plasma protein that binds heme with extraordinary affinity, blocks these effects and has been proposed as a possible treatment approach to decrease inflammation in critically ill patients. We studied mouse models of endotoxemia, burn wound infections and peritonitis in order to assess if a repletion strategy for hemopexin might be reasonable. We also measured hemopexin in small numbers of three patient populations that might be logical groups for hemopexin therapy: patients with sepsis and ARDS, patients with severe burns, and premature infants. Despite severe disease, mean plasma hemopexin levels were increased above baseline in each murine model. However, plasma hemopexin levels were decreased or markedly decreased in many patients in each of the three patient populations. Potentially different behavior of hemopexin in mice and humans may be important to consider when utilizing murine models to represent acute human inflammatory diseases in which heme plays a role. The findings raise the possibility that decreased hemopexin could result in insufficiently neutralized or cleared heme in some patients with ARDS, burns, or in premature infants who might be candidates to benefit from hemopexin administration. The online version of this article (doi:10.1186/s13054-015-0885-x) contains supplementary material, which is available to authorized users.
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影响因子：
5.7
作者：
Valentine, Catherine H.;Hellman, Judith;Warren, H. Shaw
通讯作者：
Warren, H. Shaw
影响因子：
3.7
作者：
Diepold M;Noellke P;Duffner U;Kontny U;Berner R
通讯作者：
Berner R
DOI：
10.1073/pnas.1222878110
发表时间：
2013-02-26
影响因子：
11.1
作者：
Seok, Junhee;Warren, H. Shaw;Tompkins, Ronald G.
通讯作者：
Tompkins, Ronald G.
DOI：
10.1186/cc11425
发表时间：
2012-07-16
期刊：
Critical care (London, England)
影响因子：
--
作者：
Adamzik M;Hamburger T;Petrat F;Peters J;de Groot H;Hartmann M
通讯作者：
Hartmann M
影响因子：
15.9
作者：
Chung, Su Wol;Liu, Xiaoli;Perrella, Mark A.
通讯作者：
Perrella, Mark A.