The responses of macrophages in interaction with neutrophils that undergo NETosis
The responses of macrophages in interaction with neutrophils that undergo NETosis
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DOI：
10.1016/j.jaut.2015.08.018
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发表时间：
2016-02-01
影响因子：
12.8
通讯作者：
Ishizu, Akihiro
中科院分区：
文献类型：
--
作者：
Nakazawa, Daigo;Shida, Haruki;Ishizu, Akihiro
中性粒细胞胞外陷阱（NETs）是由抗微生物蛋白修饰的网状染色质纤维，其从垂死的中性粒细胞释放。伴随NET形成的中性粒细胞死亡称为NETosis。尽管NET在天然免疫中发挥重要作用，特别是在消除微生物方面，但另一方面，DNA和胞质/核内蛋白质的胞外释放可导致宿主的各种不利因素。因此，NETosis在体内得到充分调节。目前，两种机制，即依赖于DNase I的消化和巨噬细胞的吞噬作用，已被证明是这种调节机制。在这项研究中，我们专注于经历NETosis的巨噬细胞和中性粒细胞的相互作用。结果表明，巨噬细胞表现出表型依赖性的反应后，NET的降解。相互作用后数小时，M2巨噬细胞诱导促炎反应，而M1巨噬细胞发生细胞死亡和核去致密化。M1巨噬细胞的这种核去致密化以肽基精氨酸脱亚胺酶4依赖性方式发生，并导致细胞外DNA的局部释放。此后，M1巨噬细胞以半胱天冬酶激活的DNA酶依赖性方式降解源自自身的DNA，导致细胞外DNA在24 h内清除。这种短暂的增加和随后的细胞外DNA清除机制似乎非常合理的双刃剑一样的属性。这些发现表明巨噬细胞对NETosis具有一种新的表型和时间依赖性调节。(C)2015作者爱思唯尔有限公司出版
Neutrophil extracellular traps (NETs) are net-like chromatin fibers decorated with antimicrobial proteins, which are released from dying neutrophils. The death of neutrophils with NET formation is called NETosis. Although NETs play important roles in the innate immunity, especially in the elimination of microbes, the extracellular release of DNA and intra-cytoplasmic/nuclear proteins can, on the other hand, result in diverse adversities to the hosts. Therefore, NETosis is adequately regulated in vivo. Currently, two mechanisms, namely DNase I-dependent digestion and phagocytosis by macrophages, have been shown as such regulatory mechanisms. In this study, we focused on the interaction of macrophages and neutrophils that underwent NETosis. Results demonstrated that macrophages displayed a phenotype dependent response after degradation of NETs. Several hours after the interaction, M2 macrophages induced a pro-inflammatory response, while M1 macrophages underwent cell death with nuclear decondensation. This nuclear decondensation of M1 macrophages occurred in a peptidylarginine deiminase 4-dependent manner and resulted in a local release of extracellular DNA. Thereafter, M1 macrophages degraded DNA derived from themselves in a caspase-activated DNase-dependent manner resulting in the clearance of extracellular DNA within 24 h. This transient increase and subsequent clearance mechanism of extracellular DNA seems very reasonable in terms of the double-edged sword-like property of NETs. The collective findings demonstrate a novel phenotype- and time-dependent regulation of NETosis by macrophages. (C) 2015 The Authors. Published by Elsevier Ltd.