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首页> 外文期刊>Infection and immunity >Hemoglobin increases mortality from bacterial endotoxin.
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Hemoglobin increases mortality from bacterial endotoxin.

机译：血红蛋白会增加细菌内毒素的死亡率。

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Cell-free hemoglobin (Hb) is being developed as an erythrocyte substitute. We have previously demonstrated that cell-free Hb is an endotoxin-binding protein which disaggregates endotoxin and subsequently increases the biological activity of endotoxin in several in vitro assays. Because much of the morbidity and mortality associated with gram-negative bacterial infection is the result of pathophysiologic responses to bacterial lipopolysaccharide (LPS; endotoxin), we studied the effect of Hb on LPS-mediated mortality. Hb infused intravenously into mice before, coincident with, or after intraperitoneal LPS injection substantially increased LPS-related mortality from <5% to 50 to 70% 24 h after administration of LPS and from 50% to 60 to 90% at 48 h. Enhanced mortality was observed over a range of doses of injected LPS. At a given LPS dose, enhancement of mortality was shown to be dependent on the dose of Hb administered. Unmodified native human Hb, alpha-alpha-cross-linked human Hb, and beta-beta-cross-linked human or bovine Hb all were shown to enhance LPS-mediated mortality. Depressed reticuloendothelial cell function may have contributed to the enhanced mortality from LPS in the presence of Hb. Therefore, Hb-based blood substitutes, which are currently undergoing clinical trials, may intensify the potentially fatal effects of the sepsis syndrome in patients with trauma, infection, or hypotension who receive Hb for erythrocyte replacement.
机译：无细胞血红蛋白（Hb）正在开发为红细胞替代品。先前我们已经证明，无细胞的Hb是一种内毒素结合蛋白，可分解内毒素，并随后在几种体外测定中增加内毒素的生物活性。因为与革兰氏阴性细菌感染相关的大部分发病率和死亡率是对细菌脂多糖（LPS;内毒素）的病理生理反应的结果，所以我们研究了Hb对LPS介导的死亡率的影响。在腹腔内注射LPS之前，同时或之后，向小鼠静脉内注射Hb可使LPS相关的死亡率从LPS给药后24小时的<5％增至50％至70％，在48 h的情况下从50％增至60％至90％。在注射的LPS剂量范围内观察到死亡率增加。在给定的LPS剂量下，死亡率的增加取决于所施用的Hb剂量。未修饰的天然人血红蛋白，α-α交联的人血红蛋白和β-β交联的人或牛血红蛋白均显示可提高LPS介导的死亡率。存在Hb时，网状内皮细胞功能降低可能导致LPS死亡率增加。因此，目前正在临床试验中的基于Hb的血液替代品可能会增强败血症综合征对接受Hb替代红细胞的外伤，感染或低血压患者的潜在致命影响。

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