Anti-endotoxin properties of cationic host defence peptides and proteins
Anti-endotoxin properties of cationic host defence peptides and proteins
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DOI：
10.1179/096805105x37394
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Hancock, REW
中科院分区：
文献类型：
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作者：
Bowdish, DME;Hancock, REW
哺乳动物的先天免疫系统包含一系列具有正电荷和两亲性结构的肽，其在宿主防御中具有多种重要性质。虽然这些通常被称为阳离子抗菌肽，但它们在所有复杂的生命物种中的先天防御中具有许多作用，因此我们更喜欢将它们称为宿主防御肽。这些角色包括：（i）直接杀死微生物（从细菌到病毒、真菌、寄生虫和蠕虫）的能力;（ii）在适应性反应中的佐剂活性;和（iii）在调节先天免疫中的多种作用，包括刺激保护性先天免疫同时抑制有害的炎症/脓毒性反应的明显能力。后一种性质可能是这些肽在体内的更重要的活性之一。天然免疫被认为是由保守的细菌组分与宿主细胞上的特定受体（包括Toll样受体（TLR））的相互作用触发的。然而，通过这一途径启动先天免疫应答可能会引发促炎级联反应，这是导致败血症等有害疾病的主要原因。由于我们每天都接触到潜在的危险病原体，宿主的反应必须包含一定的制衡。我们认为宿主防御肽在正常（低病原体暴露）条件下对炎症的反馈调节中起作用。本文综述了宿主防御肽的抗内毒素/抗炎特性的现有信息，并将讨论这种潜力是否可用于脓毒症的治疗益处。
The innate immune system of mammals contains a series of peptides with overall positive charge and an amphipathic structure which have a variety of important properties in host defences. Although these are often termed cationic antimicrobial peptides, they have numerous roles in innate defences in all complex species of life and thus we prefer to refer to them as host defence peptides. These roles include: (i) an ability to kill micro-organisms directly, ranging from bacteria to viruses, fungi, parasites and helminths; (ii) an adjuvant activity in the adaptive response; and (iii) a multiplicity of roles in modulating innate immunity, including an apparent ability to stimulate protective innate immunity while suppressing harmful inflammatory/septic responses. This latter property may be one of the more important activities of these peptides in vivo. Innate immunity is thought to be triggered by the interaction of conserved bacterial components with particular receptors including Toll-like receptors (TLRs) on host cells. However, the initiation of the innate immune response through this route may trigger a pro-inflammatory cascade that is the principle cause of harmful conditions such as sepsis. Since we are exposed to potentially dangerous pathogens on a daily basis, the host response must contain certain checks and balances. We propose that host defence peptides have a role in feed-back modulation of inflammation under normal (low-pathogen exposure) conditions. This review surveys the available information regarding the anti-endotoxic/anti-inflammatory properties of host defence peptides, and will address whether this potential might be exploited for therapeutic benefit in sepsis.