Circulating Histones in Sepsis: Potential Outcome Predictors and Therapeutic Targets

Li, Yupei; Wan, Dingyuan; Luo, Xinyao; Song, Tao; Wang, Yiran; Ye, Qiao; Jiang, Luojia; Liao, Ri-Qiang; Zhao, Weifeng; Su, Baihai

doi:10.3389/fimmu.2021.650184

Cited by 51 publications

(71 citation statements)

References 132 publications

(207 reference statements)

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“…It is well-documented that neutrophils are key factors in the cytokine storm and thrombotic complications experienced by COVID-19 patients and that therapeutic targeting of neutrophils might ameliorate hyperinflammatory syndrome in COVID-19. Therefore, several studies proposed that NETs could be a therapeutic target in COVID-19 patients (Table 3) [90][91][92][93].…”

Section: Neutrophils Nets and Therapeutical Interventions In Covid-19mentioning

confidence: 99%

The Emerging Role of Neutrophils in the Pathogenesis of Thrombosis in COVID-19

Iliadi

Konstantinidou

Aftzoglou

et al. 2021

IJMS

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Previous studies have shown that COVID-19 leads to thrombotic complications, which have been associated with high morbidity and mortality rates. Neutrophils are the largest population of white blood cells and play a pivotal role in innate immunity. During an infection, neutrophils migrate from circulation to the infection site, contributing to killing pathogens. This mechanism is regulated by chemokines such as IL-8. Moreover, it was shown that neutrophils play an important role in thromboinflammation. Through a diverse repertoire of mechanisms, neutrophils, apart from directly killing pathogens, are able to activate the formation of thrombi. In COVID-19 patients, neutrophil activation promotes neutrophil extracellular trap (NET) formation, platelet aggregation, and cell damage. Furthermore, neutrophils participate in the pathogenesis of endothelitis. Overall, this review summarizes recent progress in research on the pathogenesis of COVID-19, highlighting the role of the prothrombotic action of neutrophils in NET formation.

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Section: Neutrophils Nets and Therapeutical Interventions In Covid-19mentioning

confidence: 99%

The Emerging Role of Neutrophils in the Pathogenesis of Thrombosis in COVID-19

Iliadi

Konstantinidou

Aftzoglou

et al. 2021

IJMS

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“…Histones are nuclear proteins that function as packagers of nuclear DNA into chromatin [ 64 ]. In various diseases including sepsis, circulating histone levels are increased in the blood, which is why histones can be considered as a potential disease biomarker [ 65 , 66 ]. Outside the nucleus, histones act as DAMPs because they interact with TLRs and thereby induce inflammatory pathways in the target cells [ 59 , 67 ].…”

Section: Ev Functions In Sepsismentioning

confidence: 99%

Extracellular Vesicles: A Double-Edged Sword in Sepsis

2021

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Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. Several studies on mouse and patient sepsis samples have revealed that the level of extracellular vesicles (EVs) in the blood is altered compared to healthy controls, but the different functions of EVs during sepsis pathology are not yet completely understood. Sepsis EVs are described as modulators of inflammation, lymphocyte apoptosis, coagulation and organ dysfunction. Furthermore, EVs can influence clinical outcome and it is suggested that EVs can predict survival. Both detrimental and beneficial roles for EVs have been described in sepsis, depending on the EV cellular source and the disease phase during which the EVs are studied. In this review, we summarize the current knowledge of EV sources and functions during sepsis pathology based on in vitro and mouse models, as well as patient samples.

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“…This negatively charged polymer can interact with positively charged histones released by NETs, rendering them unable to activate platelets and potentiate thrombosis 31 . Furthermore, heparin can activate DNAse I and bind P-selectin and ICAM-1 to reduce the interaction and binding of platelets and neutrophils to each other and to endothelial cells 30 , 32 .…”

Section: Discussionmentioning

confidence: 99%

Coronavirus Disease 2019 (COVID-19) Coronary Vascular Thrombosis

Johnson

McGuone

et al. 2022

The American Journal of Pathology

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Severe COVID-19 infection increases the risk of myocardial injury that contributes to mortality. We used multiparameter immunofluorescence to examine extensively heart autopsy tissue of 7 patients who died of COVID-19 compared to 12 control specimens, some with and some without cardiovascular disease. Consistent with prior reports, we found no evidence of viral infection or lymphocytic infiltration indicative of myocarditis but did observe frequent and extensive thrombosis in large and small vessels in the hearts of the COVID cohort, findings that were infrequent in controls. The endothelial lining of thrombosed vessels typically lacked evidence of cytokine-mediated endothelial activation, assessed as nuclear expression of transcription factors p65 (RelA), pSTAT1, or pSTAT3 or evidence of inflammatory activation assessed by expression of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tissue factor, or von Willebrand factor (VWF). Intimal EC lining was also generally preserved with little evidence of cell death or desquamation. In contrast, there were frequent markers of neutrophil activation within myocardial thrombi of COVID-infected patients including neutrophil-platelet aggregates, neutrophil-rich clusters within macrothrombi, and evidence of neutrophil extracellular trap (NET) formation. These findings point to alterations in circulating neutrophils rather than the endothelium as contributors to the increased thrombotic diathesis in the hearts of COVID-19 patients.

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Circulating Histones in Sepsis: Potential Outcome Predictors and Therapeutic Targets

Cited by 51 publications

References 132 publications

The Emerging Role of Neutrophils in the Pathogenesis of Thrombosis in COVID-19

The Emerging Role of Neutrophils in the Pathogenesis of Thrombosis in COVID-19

Extracellular Vesicles: A Double-Edged Sword in Sepsis

Coronavirus Disease 2019 (COVID-19) Coronary Vascular Thrombosis

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