Science TM：血色素加重细菌感染

　　一项新的研究报告说，一种叫做血色素的含铁化合物会加重血液中的细菌感染，但是一种叫做血色素结合蛋白的清道夫蛋白可以清除游离的血色素并保护小鼠免受其有害的影响。

　　这些发现可能给人们带来监控败血症患者的新方法。败血症是一种血流中出现巨量的细菌并使机体免疫系统受到严重削弱的感染，它会导致血压的突然下降以及主要器官的衰竭。 检测败血症患者体内的血色素和血色素结合蛋白可帮助医师预测哪些病人在一开始的时候就需要接受更为积极的治疗。 另外，高危病患可能在被施予血色素结合蛋白或其它可消灭血色素的物质后而可能使他们免于死亡。

　　在败血症时，被称作红血球的红细胞通常会受到损伤。 当红血球裂解之后，血红蛋白被释放出来并会分解，从而将游离的血色素释放到血流之中。 正如Rasmus Larsen及其同事现在所报告的，这种游离的血色素并非一种无辜的局外旁观者。 它实际上会刺激炎症，促使细胞死亡，加重器官损害并增加患者的死亡风险。 研究人员发现，缺乏分解血红蛋白酶的小鼠其循环血液中会比正常小鼠的血液中有更多的血色素，从而使它们更容易死于败血症。 此外，该团队证明，血色素结合蛋白（这是机体产生的一种可清除游离血色素的蛋白）可保护败血症小鼠免受血色素的有害影响，从而降低其发生并发症和死亡的风险。 人们下一步需要做的是在人体内测试血色素结合蛋白是否会有同样的保护性功效。

　　推荐英文摘要：

　　Sci Transl Med  DOI: 10.1126/scitranslmed.3001118

　　A Central Role for Free Heme in the Pathogenesis of Severe Sepsis

　　Rasmus Larsen1, Raffaella Gozzelino1, Viktória Jeney1, László Tokaji1, Fernando A. Bozza2,3, André M. Japiassú2,3, Dolores Bonaparte1, Moisés Marinho Cavalcante1,*, ?ngelo Chora1, Ana Ferreira1, Ivo Marguti1, Sílvia Cardoso1, Nuno Sepúlveda1,4, Ann Smith5 and Miguel P. Soares1,?

　　Low-grade polymicrobial infection induced by cecal ligation and puncture is lethal in heme oxygenase-1–deficient mice (Hmox1?/?), but not in wild-type (Hmox1+/+) mice. Here we demonstrate that the protective effect of this heme-catabolizing enzyme relies on its ability to prevent tissue damage caused by the circulating free heme released from hemoglobin during infection. Heme administration after low-grade infection in mice promoted tissue damage and severe sepsis. Free heme contributed to the pathogenesis of severe sepsis irrespective of pathogen load, revealing that it compromised host tolerance to infection. Development of lethal forms of severe sepsis after high-grade infection was associated with reduced serum concentrations of the heme sequestering protein hemopexin (HPX), whereas HPX administration after high-grade infection prevented tissue damage and lethality. Finally, the lethal outcome of septic shock in patients was also associated with reduced HPX serum concentrations. We propose that targeting free heme by HPX might be used therapeutically to treat severe sepsis.