Presence of neutrophil extracellular traps and citrullinated histone H3 in the bloodstream of critically ill patients.
Presence of neutrophil extracellular traps and citrullinated histone H3 in the bloodstream of critically ill patients.
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DOI：
10.1371/journal.pone.0111755
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Shimazu T
中科院分区：
文献类型：
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作者：
Hirose T;Hamaguchi S;Matsumoto N;Irisawa T;Seki M;Tasaki O;Hosotsubo H;Yamamoto N;Yamamoto K;Akeda Y;Oishi K;Tomono K;Shimazu T
神经元细胞外陷阱（NETs）是一种新发现的免疫机制，由炎症刺激诱导。瓜氨酸对组蛋白H3的修饰被认为参与了NET的体外形成。本研究的目的是评估NET和瓜氨酸化组蛋白H3（Cit-H3）是否存在于危重患者的血流中，并确定与临床和生物学参数的相关性。在2011年4月至6月入住ICU时，从插管患者中采集血液样本。为了鉴定NET，在血涂片中通过免疫荧光同时观察DNA和组蛋白H3。使用特异性抗体检测Cit-H3。我们评估了NET和Cit-H3的存在与气管抽吸物中细菌的存在、SIRS、诊断、WBC计数以及IL-8、TNF-α、cf-DNA、乳酸盐和HMGB 1浓度的关系。纳入49例患者。年龄中位数为66.0岁（IQR：52.5-76.0）。诊断包括创伤（7，14.3%）、感染（14，28.6%）、心肺骤停复苏（8，16.3%）、急性中毒（4，8.1%）、心脏病（4，8.1%）、脑卒中（8，16.3%）、中暑（2，4.1%）和其他（2，4.1%）。我们在5名患者中鉴定了NET，在11名患者中鉴定了Cit-H3。在“气管吸出物中存在细菌”组（11/22，50.0%）中观察到NETs和/或Cit-H3比“气管吸出物中不存在细菌”组（4/27，14.8%）更频繁（p<0.01）。多元逻辑回归分析显示，只有气管吸出物中细菌的存在与NET和/或Cit-H3的存在显著相关。气管吸出物中细菌的存在可能是与NET形成相关的一个重要因素。NET可能在潜在感染患者的病原体从呼吸道传播到血液的生物防御中发挥关键作用。
Neutrophil extracellular traps (NETs), a newly identified immune mechanism, are induced by inflammatory stimuli. Modification by citrullination of histone H3 is thought to be involved in the in vitro formation of NETs. The purposes of this study were to evaluate whether NETs and citrullinated histone H3 (Cit-H3) are present in the bloodstream of critically ill patients and to identify correlations with clinical and biological parameters. Blood samples were collected from intubated patients at the time of ICU admission from April to June 2011. To identify NETs, DNA and histone H3 were visualized simultaneously by immunofluorescence in blood smears. Cit-H3 was detected using a specific antibody. We assessed relationships of the presence of NETs and Cit-H3 with the existence of bacteria in tracheal aspirate, SIRS, diagnosis, WBC count, and concentrations of IL-8, TNF-α, cf-DNA, lactate, and HMGB1. Forty-nine patients were included. The median of age was 66.0 (IQR: 52.5–76.0) years. The diagnoses included trauma (7, 14.3%), infection (14, 28.6%), resuscitation from cardiopulmonary arrest (8, 16.3%), acute poisoning (4, 8.1%), heart disease (4, 8.1%), brain stroke (8, 16.3%), heat stroke (2, 4.1%), and others (2, 4.1%). We identified NETs in 5 patients and Cit-H3 in 11 patients. NETs and/or Cit-H3 were observed more frequently in “the presence of bacteria in tracheal aspirate” group (11/22, 50.0%) than in “the absence of bacteria in tracheal aspirate” group (4/27, 14.8%) (p<.01). Multiple logistic regression analysis showed that only the presence of bacteria in tracheal aspirate was significantly associated with the presence of NETs and/or Cit-H3. The presence of bacteria in tracheal aspirate may be one important factor associated with NET formation. NETs may play a pivotal role in the biological defense against the dissemination of pathogens from the respiratory tract to the bloodstream in potentially infected patients.
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