Circulating nucleosomes as a predictor of sepsis and organ dysfunction in critically ill patients

Chen, Qixing; Ye, Ling; Jin, Yuqi; Zhang, Ning; Lou, Tianzheng; Qiu, Zhijun; Jin, Yue; Cheng, Baoli; Fang, Xiangming

doi:10.1016/j.ijid.2012.03.007

Cited by 67 publications

(77 citation statements)

References 28 publications

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“…Nucleosomes, which are complexes formed by DNA and histone, are also excessively released from the damaged host cells that have died from apoptosis or necrosis (15,27); nucleosome levels are therefore correlated with the inflammatory response and organ dysfunction in sepsis (11,15). Circulating histones have a highly damaging effect on endothelium and tissues (10).…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of the effect of recombinant thrombomodulin on a lipopolysaccharide-induced murine sepsis model

Takehara

Murakami

Kuwahara‐Arai

et al. 2017

Experimental and Therapeutic Medicine

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Abstract.To evaluate the effect of recombinant human thrombomodulin (rTM) on sepsis, the levels of nucleosome as well as high-mobility group box 1 (HMGB1) and cytokines in sera and peritoneal fluids were measured in a mouse model of lipopolysaccharide (LPS)-induced sepsis after administration of rTM. C57BL/6 mice were intraperitoneally injected with LPS (15 mg/kg; Escherichia coli O111:B4) with or without the intravenous administration of rTM (3 mg/kg; 30 min prior to or 2 h after LPS injection). The survival rates were evaluated and levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, HMGB1 and nucleosome in sera and peritoneal fluids were analyzed by ELISA. Administration of rTM prior to or after LPS improved the survival rate of septic mice. In addition, rTM administered prior to or after LPS suppressed the level of pro-inflammatory cytokine TNF-α in sera at 1-3 h after LPS injection, whereas only the administration of rTM after LPS suppressed the levels of HMGB1 and nucleosome (late-phase mediators of sepsis) (9-12 h) in sera after the LPS injection. Furthermore, administration of rTM prior to or after LPS suppressed the level of TNF-α in the peritoneal fluids at 1-3 h after LPS injection, whereas only the administration of rTM after LPS suppressed the levels of IL-6 and MCP-1 in the peritoneal fluids at 6-9 h after LPS injection. These observations indicated that administration of rTM significantly improves the survival rate and suppresses the increased levels of TNF-α, IL-6, MCP-1, HMGB1 and nucleosome in the LPS-induced septic shock model. Thus, rTM may exert a protective action on sepsis and reduce mortality, possibly by reducing not only the levels of cytokines and chemokine but also the levels of late-phase mediators of sepsis.

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Section: Discussionmentioning

confidence: 99%

“…NETs rapidly trap and kill microbial pathogens in the blood and tissues and prevent bacterial dissemination (5)(6)(7)9,10). Simultaneously with NET formation, HMGB1 and histone are excessively released from the damaged host cells (7,9,11) and have been shown to be lethal late phase mediators of sepsis (3,(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the effect of recombinant thrombomodulin on a lipopolysaccharide-induced murine sepsis model

Takehara

Murakami

Kuwahara‐Arai

et al. 2017

Experimental and Therapeutic Medicine

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“…They activate the endonucleases by increasing intracellular calcium and cause DNA fragmentation and apoptosis in nucleus (36). Dopamine's neurotoxic and neurodegenerative effects have been shown (6)(7)(8)(9)37). These effects are associated with oxidative metabolism (10-12, 37).…”

Section: Discussionmentioning

confidence: 99%

“…The main role of the nucleosome is the packing of DNA, which controls genetic information by regulating protein access. This control mechanism of nucleosome is regulated by post-translational modifi cations like methylation, acetylation and phosphorylation of histones (8,9). During apoptosis, nucleosomes are released into the circulation by nuclear endonucleases activation (8).…”

Section: Introductionmentioning

confidence: 99%

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Elevated nucleosome level and oxidative stress in schizophrenia patients

Bahçeci¹,

Mh²,

Us³

et al. 2015

BLL

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AIM: The aim of this study was to investigate the effect of oxidative stress on nucleosome levels and its relation with the clinical features in schizophrenia patients. MATERIAL AND METHOD: Thirty schizophrenia patients and 30 healthy controls were enrolled in this study. Patients were diagnosed with schizophrenia according to the 4th edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV). The control group consisted of 30 healthy subjects matched to the patients with regard to age and gender and who had no history of any psychiatric disorder. The severity of schizophrenia symptoms in the patients was evaluated using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Severity Scale (CGI-S). Physical and neurological examinations were performed in each of the patients and controls. RESULTS: Nucleosome, total oxidant levels and OSI values were higher in schizophrenia patients than in controls (p < 0.05). There was no signifi cant difference in the total antioxidant levels. There was a positive correlation between the nucleosome level and PANSS positive subscale (p = 0.028, r = 0.402). There was a positive correlation between TAS and age (p = 0.025, r = 0.289), PANSS total (p < 0.001, r = 0.604). There was a negative correlation between OSI and PANSS total (p = 0.019, r = -0.427), PANSS positive subscale (p = 0.043, r = -0.372). There was a negative correlation between TOS and PANS total (p = 0.028, r = -0.402). CONCLUSION: In this study we found a correlation between nucleosome level and PANSS positive subscale. To our knowledge, this is the fi rst study that evaluates oxidative stress and nucleosomes released from apoptotic cells together (Tab. 2, Ref. 50). Text in PDF www.elis.sk.

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Neutrophil extracellular traps, damage‐associated molecular patterns, and cell death during sepsis

Iba

Murai

Nagaoka

et al. 2013

Acute Medicine & Surgery

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In addition to pathogen-associated molecular patterns from invasive microorganisms, alarmins, which are major components of host defense mechanisms, are involved in the pathophysiology of sepsis. In fact, the magnitude of the insult is defined according to the damage-associated molecular pattern (DAMP), which is composed of alarmins as well as pathogen-associated molecular patterns, such as those involving nucleosomes, histones, and DNA. Regarding the antimicrobial mechanism of neutrophils, an alternative non-phagocytic mechanism was first recognized as "NETosis" in 2004. In this mechanism, microorganisms are trapped and eliminated by neutrophil extracellular traps (NETs). These NETs are composed of histones and DNA that have been expelled from the nucleus as well as antimicrobial proteases, including elastase and myeloperoxidase. NETosis, a cell death pathway reported to be distinct from apoptosis, is an active area of research. As NETs are composed of deleterious substances, they are extremely harmful to the host cells once they are released into the circulating blood. Therefore, the meanings and putative roles of these components in sepsis have attracted much attention.

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Circulating nucleosomes as a predictor of sepsis and organ dysfunction in critically ill patients

Abstract: The level of circulating nucleosomes in the serum has a predictive value for sepsis and organ dysfunction and may serve as a candidate biomarker for the diagnosis/prognosis of sepsis. Further studies are warranted to confirm the present findings.

Cited by 67 publications

References 28 publications

Evaluation of the effect of recombinant thrombomodulin on a lipopolysaccharide-induced murine sepsis model

Evaluation of the effect of recombinant thrombomodulin on a lipopolysaccharide-induced murine sepsis model

Elevated nucleosome level and oxidative stress in schizophrenia patients

Neutrophil extracellular traps, damage‐associated molecular patterns, and cell death during sepsis

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