Regulation of Extracellular Chromatin Release from Neutrophils
Regulation of Extracellular Chromatin Release from Neutrophils
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DOI：
10.1159/000206974
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发表时间：
2009-01-01
影响因子：
5.3
通讯作者：
Radic, Marko
中科院分区：
文献类型：
--
作者：
Neeli, Indira;Dwivedi, Nishant;Radic, Marko
中性粒细胞使用复杂的机制来捕获和杀死入侵的微生物。一种机制需要从细胞中释放松弛的染色质。微生物被细胞外染色质捕获，并暴露于局部高浓度的杀菌化合物。我们通过测试微管和肌动蛋白细胞骨架对中性粒细胞胞外陷阱（NETS）部署的贡献来研究染色质释放的调节。将人中性粒细胞与微管蛋白聚合抑制剂诺考达唑或肌动蛋白抑制剂细胞松弛素D孵育，通过从细胞释放染色质严重降低中性粒细胞对LPS的反应能力。此外，用M1/70（一种Mac-1整合素粘附受体的单克隆抗体）预处理中性粒细胞，大大减少了染色质在NET中的部署。组蛋白脱亚氨基分析，4个核心组蛋白中的3个通过肽基精氨酸脱亚氨基酶4将精氨酸转化为瓜氨酸，显示抑制NET形成的处理也减少了组蛋白脱亚氨基。我们的数据表明，NET的形成需要功能性微管蛋白和肌动蛋白丝，并响应于Mac-1整合素的参与。由于组蛋白脱亚氨基与NET的释放相吻合，我们认为这些事件代表了中性粒细胞对感染反应的重叠机制。版权所有（C）2009 S. Karger AG，巴塞尔
Neutrophils use intricate mechanisms for capturing and killing invading microorganisms. One mechanism entails the release of relaxed chromatin from the cell. Microbes are trapped by the extracellular chromatin and exposed to high local concentrations of bactericidal compounds. We examine the regulation of chromatin release by testing the contribution of microtubules and the actin cytoskeleton to the deployment of neutrophil extracellular traps (NETS). Incubation of human neutrophils with nocodazole, a tubulin polymerization inhibitor, or cytochalasin D, an inhibitor of actin filamentation, severely diminished the ability of neutrophils to respond to LPS by releasing chromatin from the cells. In addition, pretreatment of neutrophils with M1/70, a monoclonal antibody to the Mac-1 integrin adhesion receptor, drastically reduced the deployment of chromatin into NETs. Analysis of histone deimination, the conversion of arginine to citrulline in 3 of the 4 core histones by peptidylarginine deiminase 4, revealed that the treatments inhibiting NET formation also reduced histone deimination. Our data indicate that NET formation requires functional tubulin and actin filaments and responds to engagement of Mac-1 integrins. Because histone deimination coincides with the release of NETs, we propose that these events represent overlapping mechanisms of neutrophil responses to infections. Copyright (C) 2009 S. Karger AG, Basel