Generation of blood circulating DNA: the sources, peculiarities of circulation and structure

Bryzgunova, Olga E.; Laktionov, Pavel P.

doi:10.18097/pbmc20156104409

Cited by 7 publications

(3 citation statements)

References 190 publications

(232 reference statements)

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“…Our results are of course limited by the fact that we are working with such a complex sample as human blood plasma. It is not possible to design the experiments to exclude completely the influence of changing divalent cations concentrations 31,32 during the entire experimental procedure, the presence of cfDNA hidden in plasma exosomes 33,34 or in supramolecular complexes and on cell surfaces 35 . Nevertheless, when we quantified the cfDNA isolated from NP, from the sample exposed to the entire cfDNA removal procedure but without addition of DNase Turbo and from the TP sample, we found striking gradual decrease in cfDNA levels toward the last sample.…”

Section: Discussionmentioning

confidence: 99%

Cell-free DNA in plasma as an essential immune system regulator

Korabečná

Zinková

Brynychova

et al. 2020

Sci Rep

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The cell-free DNA (cfDNA) is always present in plasma, and it is biomarker of growing interest in prenatal diagnostics as well as in oncology and transplantology for therapy efficiency monitoring. But does this cfDNA have a physiological role? Here we show that cfDNA presence and clearance in plasma of healthy individuals plays an indispensable role in immune system regulation. We exposed THP1 cells to healthy individuals’ plasma with (NP) and without (TP) cfDNA. In cells treated with NP, we found elevated expression of genes whose products maintain immune system homeostasis. Exposure of cells to TP triggered an innate immune response (IIR), documented particularly by elevated expression of pro-inflammatory interleukin 8. The results of mass spectrometry showed a higher abundance of proteins associated with IIR activation due to the regulation of complement cascade in cells cultivated with TP. These expression profiles provide evidence that the presence of cfDNA and its clearance in plasma of healthy individuals regulate fundamental mechanisms of the inflammation process and tissue homeostasis. The detailed understanding how neutrophil extracellular traps and their naturally occurring degradation products affect the performance of immune system is of crucial interest for future medical applications.

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Section: Discussionmentioning

confidence: 99%

Cell-free DNA in plasma as an essential immune system regulator

Korabečná

Zinková

Brynychova

et al. 2020

Sci Rep

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“…Because cfDNA often circulates in complexes with proteins and lipoproteins, these structures can also interact with various receptors and facilitate the penetration of cfDNA into cells [70]. Thus, it has been shown that nucleosomes can bind to cell surface proteins with molecular weights of 29 and 69 kDa [71][72][73].…”

Section: Routes Of Tumor-derived Cfdna Penetration Into Cellsmentioning

confidence: 99%

Role of Cell-Free DNA and Deoxyribonucleases in Tumor Progression

Alekseeva

Миронова

2021

IJMS

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Many studies have reported an increase in the level of circulating cell-free DNA (cfDNA) in the blood of patients with cancer. cfDNA mainly comes from tumor cells and, therefore, carries features of its genomic profile. Moreover, tumor-derived cfDNA can act like oncoviruses, entering the cells of vulnerable organs, transforming them and forming metastatic nodes. Another source of cfDNA is immune cells, including neutrophils that generate neutrophil extracellular traps (NETs). Despite the potential eliminative effect of NETs on tumors, in some cases, their excessive generation provokes tumor growth as well as invasion. Considering both possible pathological contributions of cfDNA, as an agent of oncotransformation and the main component of NETs, the study of deoxyribonucleases (DNases) as anticancer and antimetastatic agents is important and promising. This review considers the pathological role of cfDNA in cancer development and the role of DNases as agents to prevent and/or prohibit tumor progression and the development of metastases.

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“…Circulating DNA is found to be not in free state but mainly as a part of mono-and Lupusoligonucleosomes; this conclusion is based upon its particular molecular weight and binding with histones [43]. Nucleosomes can release from cells during several physiological and pathological processes, namely apoptosis, necrosis, and formation of extracellular traps.…”

Section: Normal Generation and Clearance Of Extracellular Dnamentioning

confidence: 99%

Elimination of Nucleoproteins in Systemic Lupus Erythematosus and Antinuclear Autoantibodies Production

Trofimenko¹

2017

Lupus

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The distinctive feature of systemic lupus erythematosus (SLE) is an immune reaction directed to diverse spectrum of autoantigens, which tends to change along with the disease spreading. The most common targets of the autoantibodies are protein and nucleoprotein components of cell nuclei: dsDNA, histones, nucleosomes, Sm antigen, and Ro and La antigens. Considering that the exact causes of this tolerance loss are unknown, a certain number of hypotheses are now discussed. One of the most promising is "waste disposal" concept, which makes a link between broken elimination of cellular debris, mononuclear phagocyte system dysfunction, and initiation of autoimmunity by the antigen presenting cells in SLE. This chapter concerns the ways nuclear antigens release from cells, necrosis, and apoptosis, as well as the key molecular mechanisms of transport and elimination of these antigens, its disturbances in SLE, and connection with innate immunity by mononuclear cells. Special atention is paid to nucleosomes and DNA degradation process, its principal factors (DNase I, C1q, SAP), blood DNA transportation by immune complexes, and immune stimulating action of DNA in SLE. Current pros and cons for the waste disposal concept and existing research trends in this ield are discussed.

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Generation of blood circulating DNA: the sources, peculiarities of circulation and structure

Cited by 7 publications

References 190 publications

Cell-free DNA in plasma as an essential immune system regulator

Cell-free DNA in plasma as an essential immune system regulator

Role of Cell-Free DNA and Deoxyribonucleases in Tumor Progression

Elimination of Nucleoproteins in Systemic Lupus Erythematosus and Antinuclear Autoantibodies Production

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