Antimicrobial Peptides in Human Sepsis.
Antimicrobial Peptides in Human Sepsis.
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DOI：
10.3389/fimmu.2015.00404
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发表时间：
2015
影响因子：
7.3
通讯作者：
Schuerholz T
中科院分区：
文献类型：
--
作者：
Martin L;van Meegern A;Doemming S;Schuerholz T
近100年前，抗微生物肽（AMP）被确定为先天免疫的重要组成部分。它们存在于从细菌到哺乳动物的物种中，并且可以在体液和表面上组成性地或由炎症诱导地分离。防御素具有抗革兰氏阳性菌和革兰氏阴性菌的抗菌作用以及抗病毒和抗酵母菌的作用。人嗜中性粒细胞肽（HNP）1-3和人β-防御素（HBD）1-3是人类中最重要的防御素。最近的研究表明，脓毒症中HNP 1-3和HBD-2的水平较高。杀菌/通透性增加蛋白（BPI）可减弱局部炎症反应并降低内毒素的全身毒性。此外，BPI可能反映脓毒症器官功能障碍的严重程度。在器官衰竭患者中检测到血浆乳铁蛋白升高。HNP 1-3、乳铁蛋白、BPI和肝素结合蛋白在脓毒症中增加。人乳铁蛋白肽1-11（hLF 1-11）具有抗微生物活性并调节炎症。重组形式的乳铁蛋白[talactoferrin alpha（TLF）]已被证明可以降低危重患者的死亡率。脓毒症中TLF的II/III期研究未证实这一结果。越来越多的多重耐药细菌是脓毒症治疗中的一个持续问题。此外，已知抗生素可促进促炎细胞组分的释放，从而增加脓毒症的严重程度。与抗生素相比，AMP可以杀死细菌，但也可以中和致病因子，如脂多糖。应用天然存在的AMP的障碍是它们的高肾毒性和神经毒性。因此，挑战是开发肽来有效治疗脓毒症患者而不造成伤害。本综述重点介绍了天然和合成AMP在人类和实验性脓毒症中的作用及其在治疗重症严重感染中的显着改善作用。
Nearly 100 years ago, antimicrobial peptides (AMPs) were identified as an important part of innate immunity. They exist in species from bacteria to mammals and can be isolated in body fluids and on surfaces constitutively or induced by inflammation. Defensins have anti-bacterial effects against Gram-positive and Gram-negative bacteria as well as anti-viral and anti-yeast effects. Human neutrophil peptides (HNP) 1–3 and human beta-defensins (HBDs) 1–3 are some of the most important defensins in humans. Recent studies have demonstrated higher levels of HNP 1–3 and HBD-2 in sepsis. The bactericidal/permeability-increasing protein (BPI) attenuates local inflammatory response and decreases systemic toxicity of endotoxins. Moreover, BPI might reflect the severity of organ dysfunction in sepsis. Elevated plasma lactoferrin is detected in patients with organ failure. HNP 1–3, lactoferrin, BPI, and heparin-binding protein are increased in sepsis. Human lactoferrin peptide 1–11 (hLF 1–11) possesses antimicrobial activity and modulates inflammation. The recombinant form of lactoferrin [talactoferrin alpha (TLF)] has been shown to decrease mortality in critically ill patients. A phase II/III study with TLF in sepsis did not confirm this result. The growing number of multiresistant bacteria is an ongoing problem in sepsis therapy. Furthermore, antibiotics are known to promote the liberation of pro-inflammatory cell components and thus augment the severity of sepsis. Compared to antibiotics, AMPs kill bacteria but also neutralize pathogenic factors such as lipopolysaccharide. The obstacle to applying naturally occurring AMPs is their high nephro- and neurotoxicity. Therefore, the challenge is to develop peptides to treat septic patients effectively without causing harm. This overview focuses on natural and synthetic AMPs in human and experimental sepsis and their potential to provide significant improvements in the treatment of critically ill with severe infections.