Novel role of the antimicrobial peptide LL-37 in the protection of neutrophil extracellular traps against degradation by bacterial nucleases.
Novel role of the antimicrobial peptide LL-37 in the protection of neutrophil extracellular traps against degradation by bacterial nucleases.
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抗微生物肽LL-37在保护细胞外陷阱免受细菌核酸酶降解的保护中的新作用。
DOI：
10.1159/000363699
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发表时间：
2014
影响因子：
5.3
通讯作者：
von Köckritz-Blickwede M
中科院分区：
文献类型：
--
作者：
Neumann A;Völlger L;Berends ET;Molhoek EM;Stapels DA;Midon M;Friães A;Pingoud A;Rooijakkers SH;Gallo RL;Mörgelin M;Nizet V;Naim HY;von Köckritz-Blickwede M
神经细胞外陷阱（NET）已被描述为一种基本的先天免疫防御机制。这些NET由与不同的抗菌肽（AMP）相关的核DNA骨架组成，抗菌肽能够吞噬和杀死病原体。AMP LL-37是抗菌肽家族的成员，在NET中高度存在。然而，LL-37在NET中的功能仍然未知，因为LL-37在与NET中的DNA结合时失去其抗微生物活性。使用免疫荧光显微镜，我们证明用LL-37处理的NET对S.与未处理的NET相比，金黄色葡萄球菌核酸酶降解。利用随机LL-37片段文库的生化测定表明，LL-37对核酸酶活性的阻断作用是基于AMP的阳离子特性，其促进与嗜中性粒细胞DNA的结合，从而保护其免受核酸酶的降解。与这些数据良好相关的是，阳离子AMP人β防御素-3（hBD-3）和人嗜中性粒细胞肽-1（HNP-1）显示出类似的对嗜中性粒细胞衍生的DNA的保护作用，使其免受核酸酶降解。总之，本研究证明了AMP在宿主免疫防御中的新作用：除了其对各种病原体的直接抗微生物活性外，阳离子AMP还可以稳定嗜中性粒细胞衍生的DNA或NET，使其免受细菌核酸酶降解。
Neutrophil extracellular traps (NETs) have been described as a fundamental innate immune defense mechanism. These NETs consist of a nuclear DNA backbone associated with different antimicrobial peptides (AMPs), which are able to engulf and kill pathogens. The AMP LL-37, a member of the cathelicidin family, is highly present in NETs. However, the function of LL-37 within the NETs is still unknown, since LL-37 loses its antimicrobial activity when bound to DNA in the NETs. Using immunofluorescence microscopy we demonstrate that NETs treated with LL-37 were distinctly more resistant to S. aureus nuclease degradation compared to non-treated NETs. Biochemical assays utilising a random LL-37-fragment library indicate that the blocking effect of LL-37 on nuclease activity is based on the cationic character of the AMP, which facilitates the binding to neutrophil DNA, thus protecting it from degradation by the nuclease. In good correlation to these data, the cationic AMPs human beta defensin-3 (hBD-3) and human neutrophil peptide-1 (HNP-1) showed similar protection of neutrophil-derived DNA against nuclease degradation. In conclusion, this study demonstrates a novel role of AMPs in host immune defence: Besides its direct antimicrobial activity against various pathogens, cationic AMPs can stabilise neutrophil-derived DNA or NETs against bacterial nuclease degradation.
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影响因子：
5.3
作者：
Bober, Marta;Enochsson, Charlotte;Morgelin, Matthias
通讯作者：
Morgelin, Matthias
影响因子：
2.9
作者：
Singer, VL;Jones, LJ;Haugland, RP
通讯作者：
Haugland, RP
DOI：
10.1073/pnas.0406641102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Sumby, P;Barbian, KD;Musser, JM
通讯作者：
Musser, JM
影响因子：
4.9
作者：
Turner, J;Cho, Y;Lehrer, RI
通讯作者：
Lehrer, RI
影响因子：
6.7
作者：
Urban CF;Ermert D;Schmid M;Abu-Abed U;Goosmann C;Nacken W;Brinkmann V;Jungblut PR;Zychlinsky A
通讯作者：
Zychlinsky A