Histones and chymotrypsin-like elastases play significant roles in the antimicrobial activity of tongue sole neutrophil extracellular traps
Histones and chymotrypsin-like elastases play significant roles in the antimicrobial activity of tongue sole neutrophil extracellular traps
复制标题
组蛋白和胰凝乳蛋白酶样弹性蛋白酶在舌鳎中性粒细胞胞外陷阱的抗菌活性中发挥重要作用
DOI：
10.1016/j.fsi.2017.11.004
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发表时间：
2018
影响因子：
4.7
通讯作者：
Sun Li
中科院分区：
文献类型：
--
作者：
Wen Li lian;Zhao Ming li;Chi Heng;Sun Li
中性粒细胞胞外陷阱（NETs）是在高等和低等脊椎动物中观察到的中性粒细胞的胞外抗微生物结构的形式，后者包括硬骨鱼类半滑舌鳎（Cynoglossus semilaevis）。然而，鱼类NET的抗菌机制尚不清楚。在本研究中，我们研究了组蛋白和弹性蛋白酶对舌鳎NET抗菌作用的潜在贡献。为此目的，两个组蛋白（CsH_2B和CsH_4）和两个弹性蛋白酶（CsEla_1和CsEla_2）的舌鳎进行了研究。组蛋白和弹性蛋白酶分别具有组蛋白H2 B/H4和胰蛋白酶样丝氨酸蛋白酶的保守结构域特征。重组CsH 2B、CsH 4、CsEla 1和CsEla 2结合广泛的革兰氏阴性和革兰氏阳性细菌，并且一些结合的细菌的生长被结合的组蛋白/弹性蛋白酶抑制。CsH_2B、CsH_4、CsEla_1和CsEla_2均定位于各种刺激物（包括细菌病原体）诱导的NETs中。用靶向CsH 2B、CsH 4、CsEla 1和CsEla 2的抗体处理NET显著降低了NET的抗微生物作用。这些结果表明，组蛋白和糜蛋白酶样弹性蛋白酶是硬骨鱼NETs的基本组成部分，在NETs的抗菌活性中发挥重要作用。
Neutrophil extracellular traps (NETs) are a form of extracellular antimicrobial structure of neutrophils observed in higher and lower vertebrates, the latter including the teleost fish tongue sole Cynoglossus semilaevis. However, the antimicrobial mechanism of fish NETs is unknown. In the present study, we examined the potential contribution of histones and elastases to the antibacterial effect of tongue sole NETs. For this purpose, two histones (CsH2B and CsH4) and two elastases (CsEla1 and CsEla2) of tongue sole were investigated. The histones and elastases possess the conserved domain structures characteristic of that of histones H2B/H4 and trypsin-like serine protease, respectively. Recombinant CsH2B, CsH4, CsEla1, and CsEla2 bound a wide range of Gram-negative and Gram-positive bacteria, and some of the bound bacteria were inhibited in growth by the bound histones/elastases. CsH2B, CsH4, CsEla1, and CsEla2 were all localized in NETs induced by various stimuli including bacterial pathogen. Treatment of NETs with antibodies targeting CsH2B, CsH4, CsEla1, and CsEla2 significantly reduced the antimicrobial effect of NETs. These results indicate that histones and chymotrypsin-like elastases are fundamental components of teleost NETs that play important roles in the antimicrobial activity of NETs.