Abstract
Extracellular DNA (ecDNA) is studied as a possible biomarker, but also as a trigger of the immune responses important for the pathogenesis of several diseases. Extracellular deoxyribonuclease (DNase) activity cleaves ecDNA. The aim of our study was to describe the interindividual variability of ecDNA and DNase activity in the plasma of healthy mice, and to analyze the potential determinants of the variability, including sex, age, and bodyweight. In this experiment, 58 adult CD1 mice (41 females and 31 males) of a variable age (3 to 16 months old) and bodyweight (females 25.7 to 52.1 g, males 24.6 to 49.6 g) were used. The plasma ecDNA was measured using a fluorometric method. The nuclear ecDNA and mitochondrial ecDNA were quantified using real-time PCR. The deoxyribonuclease activity was assessed using the single radial enzyme diffusion method. The coefficient of variance for plasma ecDNA was 139%, and for DNase 48%. Sex differences were not found in the plasma ecDNA (52.7 ± 73.0 ηg/mL), but in the DNase activity (74.5 ± 33.5 K.u./mL for males, and 47.0 ± 15.4 K.u./mL for females). There were no associations between plasma ecDNA and bodyweight or the age of mice. Our study shows that the variability of plasma ecDNA and DNase in adult healthy mice is very high. Sex, age, and bodyweight seem not to be major determinants of ecDNA variability in healthy mice. As ecDNA gains importance in the research of several diseases, it is of importance to understand its production and cleavage. Further studies should, thus, test other potential determinants, taking into account cleavage mechanisms other than DNase.
Highlights
Extracellular DNA is DNA outside of cells
Donor DNA can be detected in the blood of the transplant recipient, suggesting that Extracellular DNA (ecDNA) could be a biomarker of transplant rejection [7,8]
It has been shown that ecDNA leads to inflammation and a release of more ecDNA—this vicious circle can be stopped by the removal of ecDNA, as shown for sepsis [9], hepatorenal injury [10], and metabolic syndrome [11,12]
Summary
Extracellular DNA (ecDNA) is DNA outside of cells. The presence of ecDNA in blood was discovered by Mandel and Metais in 1948 [1]. The ecDNA is proinflammatory [2] and procoagulatory [3]. Apoptosis and necrosis are the major sources of ecDNA [4]. EcDNA is used as a biomarker in non-invasive prenatal diagnostics [5] and oncology [6]. Donor DNA can be detected in the blood of the transplant recipient, suggesting that ecDNA could be a biomarker of transplant rejection [7,8]. It has been shown that ecDNA leads to inflammation and a release of more ecDNA—this vicious circle can be stopped by the removal of ecDNA, as shown for sepsis [9], hepatorenal injury [10], and metabolic syndrome [11,12]
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