Volume 11, Issue 4 (Vol.11 No.4 Jan 2023)                   rbmb.net 2023, 11(4): 577-589 | Back to browse issues page


XML Print


Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia.
Abstract:   (1523 Views)
Background: Double-stranded fragmented extracellular DNA is a participant, inducer, and indicator of various processes occurring in the organism. When investigating the properties of extracellular DNA, the question regarding the specificity of exposure to DNA from different sources has always been raised. The aim of this study was to perform comparative assessment of biological properties of double-stranded DNA obtained from the human placenta, porcine placenta and salmon sperm.

Methods: The intensity of leukocyte-stimulating effect of different dsDNA was assessed in mice after cyclophosphamide-induced cytoreduction. The stimulatory effect of different dsDNA on maturation and functions of human dendritic cells and the intensity of cytokine production by human whole blood cells was analyzed ex vivo. The oxidation level of the dsDNA was also compared.

Results: Human placental DNA exhibited the strongest leukocyte-stimulating effect. DNA extracted from human and porcine placenta exhibited similar stimulatory action on maturation of dendritic cells, allostimulatory capacity, and ability of dendritic cells to induce generation of cytotoxic CD8+CD107a+ T cells in the mixed leukocyte reaction. DNA extracted from salmon sperm stimulated the maturation of dendritic cells, while having no effect on their allostimulatory capacity. DNA extracted from human and porcine placenta was shown to exhibit a stimulatory effect on cytokine secretion by human whole blood cells. The observed differences between the DNA preparations can be caused by the total methylation level and are not related to differences in oxidation level of DNA molecules.

Conclusions: Human placental DNA exhibited the maximum combination of all biological effects.
Full-Text [PDF 448 kb]   (1091 Downloads)    
Type of Article: Original Article | Subject: Molecular Biology
Received: 2022/07/30 | Accepted: 2022/10/9 | Published: 2023/04/3

References
1. Iwasaki A, Medzhitov R. Regulation of adaptive immunity by the innate immune system. Science. 2010;327(5963):291-5. [DOI:10.1126/science.1183021] [PMID] [PMCID]
2. Pisetsky DS. The origin and properties of extracellular DNA: from PAMP to DAMP. Clin Immunol. 2012;144(1):32-40. [DOI:10.1016/j.clim.2012.04.006] [PMID] [PMCID]
3. Hartmann G. Nucleic Acid Immunity. Adv Immunol. 2017;133:121-69. [DOI:10.1016/bs.ai.2016.11.001] [PMID] [PMCID]
4. Torabi A, Tahmoorespour M, Vahedi F, Mosavari N, Nassiri M. Construction of eukaryotic expression vectors encoding CFP-10 and ESAT-6 genes and their potential in lymphocyte proliferation. Rep Biochem Mol Biol. 2013;2(1):35-41.
5. Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, Knippers R. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res. 2001;61(4):1659-65.
6. Choubey D. DNA-responsive inflammasomes and their regulators in autoimmunity. Clin Immunol. 2012;142(3):223-31. [DOI:10.1016/j.clim.2011.12.007] [PMID] [PMCID]
7. Ermakov AV, Konkova MS, Kostyuk SV, Egolina NA, Efremova LV, Veiko NN. Oxidative stress as a significant factor for development of an adaptive response in irradiated and nonirradiated human lymphocytes after inducing the bystander effect by low-dose X-radiation. Mutat Res. 2009;669(1-2):155-61. [DOI:10.1016/j.mrfmmm.2009.06.005] [PMID]
8. Pugin J. How tissue injury alarms the immune system and causes a systemic inflammatory response syndrome. Ann Intensive Care. 2012;2(1):27. [DOI:10.1186/2110-5820-2-27] [PMID] [PMCID]
9. Zou L. Single- and double-stranded DNA: building a trigger of ATR-mediated DNA damage response. Genes Dev. 2007;21(8):879-85. [DOI:10.1101/gad.1550307] [PMID]
10. Dolgova EV, Proskurina AS, Nikolin VP, Popova NA, Alyamkina EA, Orishchenko KE, et al. "Delayed death" phenomenon: A synergistic action of cyclophosphamide and exogenous DNA. Gene. 2012;495(2):134-45. [DOI:10.1016/j.gene.2011.12.032] [PMID]
11. Ritter GS, Nikolin VP, Popova NA, Proskurina AS, Kisaretova PE, Taranov OS, et al. Characterization of biological peculiarities of the radioprotective activity of double-stranded RNA isolated from Saccharomyces сerevisiae. Int J Radiat Biol. 2020 Sep;96(9):1173-1191. [DOI:10.1080/09553002.2020.1793020] [PMID]
12. Dempsey A, Bowie AG. Innate immune recognition of DNA: A recent history. Virology. 2015;479-480:146-52. [DOI:10.1016/j.virol.2015.03.013] [PMID] [PMCID]
13. Vahedi F, Ghorbani E, Falsafi T. Construction of an expression plasmid (vector) encoding Brucella melitensis outer membrane protein, a candidate for DNA vaccine. Rep Biochem Mol Biol. 2013;1(2):82-6.
14. Yakubov LA, Rogachev VA, Likhacheva AC, Bogachev SS, Sebeleva TE, Shilov AG, et al. Natural human gene correction by small extracellular genomic DNA fragments. Cell Cycle. 2007;6(18):2293-301. [DOI:10.4161/cc.6.18.4729] [PMID]
15. García-Olmo DC, Picazo MG, García-Olmo D. Transformation of non-tumor host cells during tumor progression: Theories and evidence. Expert Opin Biol Ther. 2012; 12 Suppl 1:S199-207. [DOI:10.1517/14712598.2012.681370] [PMID]
16. Ronquist G. Prostasomes are mediators of intercellular communication: from basic research to clinical implications. J Intern Med. 2012;271(4):400-13. [DOI:10.1111/j.1365-2796.2011.02487.x] [PMID]
17. Fernando MR, Jiang C, Krzyzanowski GD, Ryan WL. New evidence that a large proportion of human blood plasma cell-free DNA is localized in exosomes. PLoS One. 2017;12(8):e0183915. [DOI:10.1371/journal.pone.0183915] [PMID] [PMCID]
18. Duvvuri B, Lood C. Cell-Free DNA as a Biomarker in Autoimmune Rheumatic Diseases. Front Immunol. 2019;10:502. [DOI:10.3389/fimmu.2019.00502] [PMID] [PMCID]
19. Ludwig AK, Giebel B. Exosomes: small vesicles participating in intercellular communication. Int J Biochem Cell Biol. 2012;44(1):11-5. [DOI:10.1016/j.biocel.2011.10.005] [PMID]
20. Alyamkina EA, Leplina OY, Ostanin AA, Chernykh ER, Nikolin VP, Popova NA, et al. Effects of human exogenous DNA on production of perforin-containing CD8+ cytotoxic lymphocytes in laboratory setting and clinical practice. Cell Immunol. 2012;276(1-2):59-66. [DOI:10.1016/j.cellimm.2012.04.004] [PMID]
21. Alyamkina EA, Leplina OY, Sakhno L V, Chernykh ER, Ostanin AA, Efremov YR, et al. Effect of double-stranded DNA on maturation of dendritic cells in vitro. Cellular Immunology. 2010;266:46-51. [DOI:10.1016/j.cellimm.2010.08.011] [PMID]
22. Alyamkina EA, Dolgova EV, Likhacheva AS, Rogachev VA, Sebeleva TE, Nikolin VP, et al. Exogenous allogenic fragmented double-stranded DNA is internalized into human dendritic cells and enhances their allostimulatory activity. Cell Immunol. 2010;262(2):120-6. [DOI:10.1016/j.cellimm.2010.01.005] [PMID]
23. Orishchenko KE, Ryzhikova SL, Druzhinina YG, Ryabicheva TG, Varaksin NA, Alyamkina EA, et al. Effect of human double-stranded DNA preparation on the production of cytokines by dendritic cells and peripheral blood cells from relatively healthy donors. Cancer Therapy. 2011;8:191-205.
24. Della Bella S, Nicola S, Riva A, Biasin M, Clerici M, Villa ML. Functional repertoire of dendritic cells generated in granulocyte macrophage-colony stimulating factor and interferon-alpha. J Leukoc Biol. 2004;75(1):106-16. [DOI:10.1189/jlb.0403154] [PMID]
25. Wrobel K, Landero Figueroa JA, Zaina S, Lund G, Wrobel K. Phosphorus and osmium as elemental tags for the determination of global DNA methylation--a novel application of high performance liquid chromatography inductively coupled plasma mass spectrometry in epigenetic studies. J Chromatogr B Analyt Technol Biomed Life Sci. 2010;878(5-6):609-14. [DOI:10.1016/j.jchromb.2010.01.008] [PMID]
26. Marmur J, Doty P. Determination of the base composition of deoxyribonucleic acid from its thermal denaturation temperature. Journal of Molecular Biology. 1962;5:109-18. [DOI:10.1016/S0022-2836(62)80066-7] [PMID]
27. Choi M, Lee J, Le MT, Nguyen DT, Park S, Soundrarajan N; et al. Genome-wide analysis of DNA methylation in pigs using reduced representation bisulfite sequencing. DNA Res. 2015;22(5):343-55. [DOI:10.1093/dnares/dsv017] [PMID] [PMCID]
28. Breiling A, Lyko F. Epigenetic regulatory functions of DNA modifications: 5-methylcytosine and beyond. Epigenetics Chromatin. 2015;8:24. [DOI:10.1186/s13072-015-0016-6] [PMID] [PMCID]
29. Ehrlich M, Gama-Sosa MA, Huang LH, Midgett RM, Kuo KC, McCune RA, Gehrke C. Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. Nucleic Acids Res. 1982;10(8):2709-21. [DOI:10.1093/nar/10.8.2709] [PMID] [PMCID]
30. Fuke C, Shimabukuro M, Petronis A, Sugimoto J, Oda T, Miura K, Miyazaki T, et al. Age related changes in 5-methylcytosine content in human peripheral leukocytes and placentas: an HPLC-based study. Ann Hum Genet. 2004;68(Pt 3):196-204. [DOI:10.1046/j.1529-8817.2004.00081.x] [PMID]
31. Sandhu J, Kaur B, Armstrong C, Talbot CJ, Steward WP, Farmer PB, Singh R. Determination of 5-methyl-2'-deoxycytidine in genomic DNA using high performance liquid chromatography-ultraviolet detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2009;877(20-21):1957-61. [DOI:10.1016/j.jchromb.2009.05.032] [PMID]
32. Jin L, Jiang Z, Xia Y, Lou P, Chen L, Wang H, et al. Genome-wide DNA methylation changes in skeletal muscle between young and middle-aged pigs. BMC Genomics. 2014;15(1):653. [DOI:10.1186/1471-2164-15-653] [PMID] [PMCID]
33. Alcazar Magana A, Wrobel K, Corrales Escobosa AR, Wrobel K. Application of liquid chromatography/electrospray ionization ion trap tandem mass spectrometry for the evaluation of global nucleic acids: Methylation in garden cress under exposure to CuO nanoparticles. Rapid Commun Mass Spectrom. 2016;30(1):209-20. [DOI:10.1002/rcm.7440] [PMID]
34. Wang X, Kadarmideen HN. An Epigenome-Wide DNA Methylation Map of Testis in Pigs for Study of Complex Traits. Front Genet. 2019;10:405. [DOI:10.3389/fgene.2019.00405] [PMID] [PMCID]
35. Kasai H, Crain PF, Kuchino Y, Nishimura S, Ootsuyama A, Tanooka H. Formation of 8-hydroxyguanine moiety in cellular DNA by agents producing oxygen radicals and evidence for its repair. Carcinogenesis. 1986;7(11):1849-51. [DOI:10.1093/carcin/7.11.1849] [PMID]
36. Griffiths HR, Møller L, Bartosz G, Bast A, Bertoni-Freddari C, Collins A, et al. Biomarkers. Mol Aspects Med. 2002;23(1-3):101-208. [DOI:10.1016/S0098-2997(02)00017-1] [PMID]
37. Slørdal L, Warren DJ, Moore MA. Effect of recombinant murine tumor necrosis factor on hemopoietic reconstitution in sublethally irradiated mice. J Immunol. 1989;142(3):833-5. [DOI:10.4049/jimmunol.142.3.833] [PMID]
38. Nakai S, Aihara K, Hirai Y. Interleukin-1 potentiates granulopoiesis and thrombopoiesis by producing hematopoietic factors in vivo. Life Sci. 1989;45(7):585-91. [DOI:10.1016/0024-3205(89)90043-X] [PMID]
39. Dolgova EV, Efremov YR, Orishchenko KE, Andrushkevich OM, Alyamkina EA, Proskurina AS, et al. Delivery and processing of exogenous double-stranded DNA in mouse CD34+ hematopoietic progenitor cells and their cell cycle changes upon combined treatment with cyclophosphamide and double-stranded DNA. Gene. 2013;528(2):74-83. [DOI:10.1016/j.gene.2013.06.058] [PMID]
40. Dolgova EV, Alyamkina EA, Efremov YR, Nikolin VP, Popova NA, Tyrinova TV, et al. Identification of cancer stem cells and a strategy for their elimination. Cancer Biol Ther. 2014;15(10):1378-94. [DOI:10.4161/cbt.29854] [PMID] [PMCID]
41. Likhacheva AS, Nikolin VP, Popova NA, Rogachev VA, Prokhorovich MA, Sebeleva TE, et al. Exogenous DNA can be captured by stem cells and be involved in their rescue from death after lethal-dose γ-radiation. Gene Ther Mol Biol. 2007;11(2):305-14.
42. Gravina S, Sedivy JM, Vijg J. The dark side of circulating nucleic acids. Aging Cell. 2016;15(3):398-9. [DOI:10.1111/acel.12454] [PMID] [PMCID]

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.