特邀综述:合成阳离子化合物中和内毒素的机制

J. Andrä, T. Gutsmann, P. Garidel, K. Brandenburg
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引用次数: 33

摘要

在重症监护病房治疗脓毒症患者的一个基本挑战是细菌致病性因子,如脂多糖(内毒素)从革兰氏阴性菌的细胞膜释放由于抗生素的杀伤。LPS聚集体可能与血清和膜蛋白(如LBP(脂多糖结合蛋白)和CD14)相互作用,导致观察到的免疫系统强烈反应。因此,对革兰氏阴性菌感染患者的有效治疗必须包括除细菌杀灭外的内毒素的中和。在这里,数据总结了合成化合物表明逐步发展到非常有效的脂多糖中和剂。这些数据包括基于天然结合蛋白(如乳铁蛋白、limus抗LPS因子、NK-lysin和cathelicidins)的内毒素结合域或基于LPS隔离多胺的合成肽。这些化合物中的许多不仅可以在体外发挥作用,而且可以在体内发挥作用。在脓毒症的动物模型中),并且可能在未来的临床试验和脓毒症治疗中有用。
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Invited review: Mechanisms of endotoxin neutralization by synthetic cationic compounds
A basic challenge in the treatment of septic patients in critical care units is the release of bacterial pathogenicity factors such as lipopolysaccharide (LPS, endotoxin) from the cell envelope of Gram-negative bacteria due to killing by antibiotics. LPS aggregates may interact with serum and membrane proteins such as LBP (lipopolysaccharide-binding protein) and CD14 leading to the observed strong reaction of the immune system. Thus, an effective treatment of patients infected by Gram-negative bacteria must comprise beside bacterial killing the neutralization of endotoxins. Here, data are summarized for synthetic compounds indicating the stepwise development to very effective LPS-neutralizing agents. These data include synthetic peptides, based on the endotoxin-binding domains of natural binding proteins such as lactoferrin, Limulus anti-LPS factor, NK-lysin, and cathelicidins or based on LPS sequestering polyamines. Many of these compounds could be shown to act not only in vitro, but also in vivo (e.g . in animal models of sepsis), and might be useful in future clinical trials and in sepsis therapy.
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