LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria
LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria
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DOI：
10.1172/jci2338
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发表时间：
1998-05-15
影响因子：
15.9
通讯作者：
Schumann, RR
中科院分区：
文献类型：
--
作者：
Lamping, N;Dettmer, R;Schumann, RR
内毒素结合蛋白(LBP)识别细菌内毒素并将其转移到CD14，从而增强宿主细胞的刺激，最终导致感染性休克等致病状态。最近，LBP在体外也被证明通过将脂多糖转移到高密度脂蛋白颗粒中来解毒。因此，LBP在体内的主要功能仍不清楚。为了研究重组小鼠LBP急性期浓度的生物学活性，对高浓度的LBP进行了体外和体内实验。尽管在小鼠巨噬细胞系中加入低浓度的LBP可促进脂多糖诱导的肿瘤坏死因子-α的合成，但与低剂量的LBP相比，急性期浓度的LBP可阻断这一作用；当LBP经小鼠腹腔注射时，可抑制脂多糖介导的细胞因子的释放，防止肝功能衰竭，从而显著降低内毒素攻击和D-氨基半乳糖致敏小鼠以及菌血症小鼠的死亡率。这些结果补充了最近的一项研究，该研究表明，与正常小鼠相比，LBP缺乏的小鼠更容易受到腹膜内沙门氏菌的感染。结论：LBP急性期对内毒素和细菌感染具有保护作用，可能是一种抗感染的生理防御机制。尽管任何小鼠脓毒症模型都有局限性，但结果表明，LBP在人类革兰氏阴性腹膜炎中可能有有益的效果。
LPS-binding protein (LBP) recognizes bacterial LPS and transfers it to CD14, thereby enhancing host cell stimulation, eventually resulting in pathogenic states such as septic shock. Recently, LBP also was shown to detoxify LPS by transferring LPS into HDL particles in vitro. Thus, the predominant in vivo function of LBP has remained unclear. To investigate the biological activity of acute phase concentrations of recombinant murine LBP, high concentrations of LBP were investigated in vitro and in vivo. Although addition of low concentrations of LBP to a murine macrophage cell line enhanced LPS-induced TNF-alpha synthesis, acute phase concentrations of LBP blocked this effect in comparison to low-dose LBP, When injected into mice intraperitoneally, LBP inhibited LPS-mediated cytokine release and prevented hepatic failure resulting in a significantly decreased mortality rate in LPS-challenged and D-galactosamine-sensitized mice, as well as in a murine model of bacteremia. These results complement a recent study revealing LBP-deficient mice to be dramatically more susceptible to an intraperitoneal Salmonella infection as compared with normal mice. We conclude that acute phase LBP has a protective effect against LPS and bacterial infection and may represent a physiologic defense mechanism against infection. Despite the limitations of any murine sepsis model, the results shown may imply that LBP could have beneficial effects during gram-negative peritonitis in humans.