Circulating Extracellular DNA: Cause or Consequence of Thrombosis?

Jiménez-Alcázar, Miguel; Kim, Natalie; Fuchs, Tobias A.

doi:10.1055/s-0036-1597284

Cited by 66 publications

(47 citation statements)

References 111 publications

(210 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been recommended to study procoagulant activity of cfDNA with the use of different DNA‐isolation techniques . Our results suggest that the high levels of circulating cfDNA during liver transplantation contribute to in vivo activation of coagulation, which is in line with clinical studies that have described the association between elevated plasma levels of cfDNA (and nucleosomes) and thrombotic diseases …”

Section: Discussionsupporting

confidence: 87%

“…These constituents together form a weblike structure, referred to as neutrophil extracellular traps (NETs), which was first described as a mechanism of pathogen entrapment and clearance . Clinical studies have shown that increased plasma levels of cfDNA and other (more specific) markers for NETs are found in patients with thrombotic diseases, such as deep vein thrombosis, myocardial infarction, and stroke, and it has been suggested that NETs form a risk factor for development of thrombotic disease . Experimental animal models have established that cfDNA and NETs are important contributors to the formation of thrombi .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Elevated Plasma Levels of Cell‐Free DNA During Liver Transplantation Are Associated With Activation of Coagulation

et al. 2018

View full text Add to dashboard Cite

Patients undergoing liver transplantation have complex changes in their hemostatic system, and the net effect of these changes appears to be a "rebalanced" hemostatic profile. Recently, a process called NETosis in which a neutrophil expels DNA and proteins that form a weblike structure, has been described as a mechanism of pathogen entrapment. Increasing evidence suggests a pivotal role for neutrophil extracellular traps (NETs) and their main component, cell-free DNA (cfDNA), in activation of coagulation. Because liver transplantation is associated with substantial (hepatocyte) cell death and intrahepatic neutrophil accumulation, NETs might play an important role in the hemostatic balance during liver transplantation. Here, we determined markers for NETs in the plasma of patients undergoing a liver transplantation and examined their association with activation of coagulation. Markers for NETs and markers for activation of coagulation were determined in serial plasma samples taken from patients undergoing a liver transplantation (n = 21) and compared with plasma levels in healthy controls. We found perioperative increases of markers for NETs with levels of cfDNA and nucleosomes that peaked after reperfusion and myeloperoxidase (MPO)-DNA complexes that peaked during the anhepatic phase. CfDNA and nucleosome levels, but not MPO-DNA levels, correlated with prothrombin fragment 1+2 and thrombin-antithrombin complex levels, which are established markers for activation of coagulation. Neutrophils undergoing NETosis were observed by immunostainings in postreperfusion biopsies. In conclusion, although NETosis occurs during liver transplantation, the majority of circulating DNA appears to be derived from cell death within the graft. The perioperative increases in cfDNA and nucleosomes might contribute to the complex hemostatic rebalance during liver transplantation.

show abstract

Section: Discussionsupporting

confidence: 87%

mentioning

confidence: 99%

Elevated Plasma Levels of Cell‐Free DNA During Liver Transplantation Are Associated With Activation of Coagulation

et al. 2018

View full text Add to dashboard Cite

show abstract

“…NET primarily identified, produced by neutrophils to kill microorganisms and to defend against pathogens, are demonstrated to be formed also during inflammatory events, as for example, in cystic fibrosis, thrombosis, and chronic obstructive pulmonary disease . In the last years, the list of diseases in which these neutrophil products are demonstrated to be involved was certainly increased and a key role of NET in non‐infective diseases was recently outlined .…”

Section: Discussionmentioning

confidence: 99%

β2-Adrenoceptors inhibit neutrophil extracellular traps in human polymorphonuclear leukocytes

Marino

Scanzano

Pulze

et al. 2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

This study tests the hypothesis that in isolated human polymorphonuclear leukocytes (PMN) adrenergic ligands can affect neutrophil extracellular trap (NET) formation. We have previously shown that, in PMN, adrenaline (A), through the activation of adrenergic receptors (AR), reduces stimulus-dependent cell activation; we have, therefore, planned to investigate if AR are involved in NET production. PMN were obtained from venous blood of healthy subject. The ability of adrenergic ligands to affect reactive oxygen species (ROS) production, NET production, and cell migration was investigated in cells cultured under resting conditions or after activation with N-formyl-methionyl-leucyl-phenylalanine (fMLP), LPS, or IL-8. Stimuli-induced NET production measured as ROS, microscopic evaluation, and elastase production was reverted by A and this effect was blocked by the selective β -AR antagonist ICI-118,551. The stimulus-induced ROS generation and migration was prevented by A and by isoprenaline (ISO), and these effects were counteracted only by ICI-118,551 and not by the other two selective ligands for the β and β -AR. Finally, the presence of the β-ARs on PMN was confirmed, by means of microscopy and flow cytometry. The data of the present study suggest that adrenergic compounds, through the interaction of mainly β -AR, are able to affect neutrophil functions. These data are suggestive of a possible therapeutic role of β -AR ligands (in addition to their classical use), promoting the possible therapeutic relevance of adrenergic system in the modulation of innate immunity proposing their possible use as anti-inflammatory drugs.

show abstract

“…5,6 The first, representing the contribution from Jiménez-Alcázar et al, 7 is on the topic of circulating extracellular DNA (ceDNA), and poses the question of whether this is the cause or consequence of thrombosis? As is well known to our readers, thrombosis leads to ischemic organ damage, and potentially arises in many disease processes.…”

mentioning

confidence: 99%