СВОБОДНАЯ ВНЕКЛЕТОЧНАЯ ДНК В НОРМЕ И ПРИ ПАТОЛОГИИ
Аннотация
Резюме. В работе представлены литературные данные о существовании в организме свободной ДНК (свДНК), не связанной с клетками, которая определяется практически во всех жидкостях организма. Данные свидетельствуют о том, что свДНК определяется в нормальном, здоровом организме. При этом повышение уровня свДНК в плазме и сыворотке крови определяется при многих заболеваниях, включая аутоиммунные заболевания, злокачественные новообразования, инфаркт миокарда и др. Во многих случаях уровень свДНК становится предиктором появления того или иного заболевания, а также утяжеления течения болезни. До сих пор не ясна физиологическая роль свДНК, а также ее значение в развитии того или иного заболевания. Показано, что свДНК может стимулировать и подавлять функции иммунокомпетентных клеток, может выполнять роль индуктора аутоиммунных состояний. Кроме того, предполагается, что свДНК может служить переносчиком генетической информации в организме между опухолевыми и нормальными клетками, так же как между последними из различных органов и тканей.
Об авторе
В. А. Козлов
ФГБУ «Научно-исследовательский институт клинической иммунологии» СО РАМН, г. Новосибирск
Россия
Россия
д.м.н., профессор, академик РАМН, директор
630090, ул. Ядринцевская, 14. Тел.: 8 (383) 222-66-27. Факс: 8 (383) 222-70-28
Список литературы
1. Arnalich F., Codoceo R., L pez-Collazo E., Montiel C. Circulating cell-free mitochondrial DNA: a better early prognostic marker in patients with out-of-hospital cardiac arrest. Resuscitation, 2012, vol. 83, no. 7, pp. 162-173.
2. Arnalich F., Men ndez M., Lagos V., Ciria E., Quesada A., Codoceo R., Vazquez J.J., L pez-Collazo E. and Montiel C. Prognostic value of cell-free plasma DNA in patients with cardiac arrest outside the hospital: an observational cohort study. Critical Care, 2010, vol. 14, R47, pp. 1-11.
3. Agostini M., Pucciarelli S., Enzo M.V., Del Bianco P., Briarava M., Bedin C., Maretto I., Friso M.L., Lonardi S., Mescoli C., Toppan P., Urso E., Nitti D. Circulating cell-free DNA: a promising marker of pathologic tumor response in rectal cancer patients receiving preoperative chemoradiotherapy. Ann. Surg. Oncol., 2011, vol. 18, no. 9, pp. 2461-2468.
4. Anker P., Stroun M. Immunological aspects of circulating DNA. Ann N. Y. Acad. Sci., 2006, vol. 1075, pp. 34-39.
5. Barrat F.J., Coffman R.L. Development of TLR inhibitors for the treatment of autoimmune diseases. Immunology Reviews, 2008, vol. 223, pp. 271-283.
6. Barton G.M., Kagan J.C., Medzhitov R. Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA. Nat. Immunol., 2006, vol. 7, no. 1, pp. 49-56.
7. Breitbach S., Tug S., Simon P. Circulating cell-free DNA: an up-coming molecular marker in exercise physiology. Sports Med., 2012, vol. 42, no. 7, pp. 565-586.
8. Chan J.Y., Chow V.L., Mok V.W., Ho A.C., Wei W.I. Prediction of surgical outcome using plasma Epstein-Barr virus dna and (18)F-FDG PET-CT scan in recurrent nasopharyngeal carcinoma. Head Neck, 2012, vol. 34, no. 4, pp. 541-545.
9. Chan K.C., Lo Y.M. Circulating tumour-derived nucleic acids in cancer patients: potential applications as tumour markers. Br. J. Cancer, 2007, vol. 12, no. 96, pp. 681-685.
10. Chang K.P., Tsang N.M., Liao C.T., Hsu C.L., Chung M.J., Lo C.W., Chan S.C., Ng S.H., Wang H.M., Yen T.C. Prognostic significance of 18F-FDG PET parameters and plasma Epstein-Barr virus DNA load in patients with nasopharyngeal carcinoma. J. Nucl. Med., 2012, vol. 53, no. 1, pp. 21-28.
11. Chimonidou M., Tzitzira A., Strati A., Sotiropoulou G., Sfikas C., Malamos N., Georgoulias V., Lianidou E. CST6 promoter methylation in circulating cell-free DNA of breast cancer patients. Clin. Biochem., 2013, vol. 46, no. 3, pp. 235-240.
12. Choi J.J., Reich C.F. 3rd, Pisetsky D.S. The role of macrophages in the in vitro generation of extracellular DNA from apoptotic and necrotic cells. Immunology, 2005, vol. 115, no. 1, pp. 55-62.
13. Dalpke A., Frank J., Peter M., Heeg K. Activation of toll-like receptor 9 by DNA from different bacterial species. Infect. Immun., 2006, vol. 74, no. 2, pp. 940-946.
14. Duramad O., Fearon K.L., Chan J.H., Kanzler H., Marshall J.D., Coffman R.L., Barrat F.J. IL-10 regulates plasmacytoid dendritic cell response to CpG-containing immunostimulatory sequences. Blood, 2003, vol. 15, no. 102, pp. 4487-4492.
15. Ellinger J., Albers P., M ller S.C., von Ruecker A., Bastian P.J. Circulating mitochondrial DNA in the serum of patients with testicular germ cell cancer as a novel noninvasive diagnostic biomarker. BJU International, 2009, vol. 104, no. 1, pp. 48-52.
16. Ellinger J., Albers P., Perabo F.G., M ller S.C., von Ruecker A., Bastian P.J. CpG island hypermethylation of cell-free circulating serum DNA in patients with testicular cancer. J. Urol., 2009, vol. 182, no. 1, pp. 324-329.
17. Ellinger J., M ller S.C., Wernert N., von Ruecker A., Bastian P.J. Mitochondrial DNA in serum of patients with prostate cancer: a predictor of biochemical recurrence after prostatectomy. BJU International, 2008, vol. 5, no. 102, pp. 628-632.
18. Favaloro B., Allocati N., Graziano V., Di Ilio C., De Laurenzi V. Role of apoptosis in disease. Aging (Albany NY), 2012, vol. 4, no. 5, pp. 330-349.
19. Gahan P.B., Swaminathan R. Circulating nucleic acids in plasma and serum. Recent developments. Ann N. Y. Acad. Sci., 2008, vol. 1137, pp. 1-6.
20. Gaipl U.S., Munoz L.E., Grossmayer G., Lauber K., Franz S., Sarter K., Voll R.E., Winkler T., Kuhn A., Kalden J., Kern P., Herrmann M. Clearance deficiency and systemic lupus erythematosus (SLE). J. Autoimmun., 2007, vol. 28, no. 2-3, pp. 114-121.
21. Garc a-Olmo D., Garc a-Olmo D.C. Functionality of circulating DNA: the hypothesis of genometastasis. Ann N. Y. Acad. Sci., 2001, vol. 945, pp. 265-275.
22. Garc a-Olmo D.C., Dom nguez C., Garc a-Arranz M., Anker P., Stroun M., Garc a-Verdugo J.M., Garc a-Olmo D. Cell-free nucleic acids circulating in the plasma of colorectal cancer patients induce the oncogenic transformation of susceptible cultured cells. Cancer Res., 2010, vol. 70, no. 2, pp. 560-567.
23. Garc a-Olmo D., Garc a-Olmo D.C., Dom nguez-Berzosa C., Guadalajara H., Vega L., Garc a-Arranz M. Oncogenic transformation induced by cell-free nucleic acids circulating in plasma (genometastasis) remains after the surgical resection of the primary tumor: a pilot study. Expert Opin. Biol. Ther., 2012, vol. 12, suppl 1, pp. 61-68.
24. Ha T.T., Huy N.T., Murao L.A., Lan N.T., Thuy T.T., Tuan H.M., Nga C.T., Tuong V.V., Dat T.V., Kikuchi M., Yasunami M., Morita K., Huong V.T., Hirayama K. Elevated levels of cell-free circulating DNA in patients with acute dengue virus infection. PLoS One, 2011, vol. 6, no. 10, p. 25969.
25. Hashad D., Sorour A., Ghazal A., Talaat I. Free circulating tumor DNA as a diagnostic marker for breast cancer. J. Clin. Lab. Anal., 2012, vol. 26, no. 6, pp. 467-472.
26. Hoque M.O., Feng Q., Toure P., Dem A., Critchlow C.W., Hawes S.E., Wood T., Jeronimo C., Rosenbaum E., Stern J., Yu M., Trink B., Kiviat N.B., Sidransky D. Detection of aberrant methylation of four genes in plasma DNA for the detection of breast cancer. J. Clin. Oncol., 2006, vol. 10, no. 24, pp. 4262-4269.
27. Jahr S., Hentze H., Englisch S., Hardt D., Fackelmayer F.O., Hesch R.D., 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, vol. 15, no. 61, pp. 1659-1665.
28. Jarnicki A.G., Conroy H., Brereton C., Donnelly G., Toomey D., Walsh K., Sweeney C., Leavy O., Fletcher J., Lavelle E.C., Dunne P., Mills K.H. Attenuating regulatory T cell induction by TLR agonists through inhibition of p38 MAPK signaling in dendritic cells enhances their efficacy as vaccine adjuvants and cancer immunotherapeutics. J. Immunol., 2008, vol. 15, no. 180, pp. 3797-3806.
29. Jin B., Sun T., Yu X.H., Yang Y.X., Yeo A.E. The effects of TLR activation on T-cell development and differentiation. Clin. Dev. Immunol., 2012. 32 p.
30. Kawane K., Ohtani M., Miwa K., Kizawa T., Kanbara Y., Yoshioka Y., Yoshikawa H., Nagata S. Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages. Nature, 2006, vol. 443, no. 7114, pp. 998-1002.
31. Kohler C., Radpour R., Barekati Z., Asadollahi R., Bitzer J., Wight E., B rki N., Diesch C., Holzgreve W., Zhong X.Y. Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors. Mol. Cancer, 2009, vol. 17, no. 8, p. 105.
32. Krieg A.M., Yi A.-K., Matson S., Waldschmidt T.J., Bishop G.A., Teasdale R., Koretzky G.A., Klinman D.M. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature, 1995, vol. 374, no. 6522, pp. 546-549.
33. Krieg A.M. Signal transduction induced by immunostimulatory CpG DNA. Springer Semin Immunopathol., 2000, vol. 22, pp. 97-105.
34. Krug A. Nucleic acid recognition receptors in autoimmunity. Handb Exp. Pharmacol., 2008, vol. 183, pp. 129-151.
35. Lam N.Y., Rainer T.H., Wong L.K., Lam W., Lo Y.M. Plasma DNA as a prognostic marker for stroke patients with negative neuroimaging within the first 24 h of symptom onset. Resuscitation, 2006, vol. 68, no. 1, pp. 71-78.
36. Lamphier M.S., Sirois C.M., Verma A., Golenbock D.T., Latz E. TLR9 and the recognition of self and nonself nucleic acids. Ann N. Y. Acad. Sci., 2006, vol. 1082, pp. 31-43.
37. Langford M.P., Redens T.B., Harris N.R., Lee S., Jain S.K., Reddy S., McVie R. Plasma levels of cell-free apoptotic DNA ladders and gamma-glutamyltranspeptidase (GGT) in diabetic children. Exp. Biol. Med. (Maywood), 2007, vol. 232, no. 9, pp. 1160-1169.
38. Lechner M.G., Epstein A.L. A new mechanism for blocking myeloid-derived suppressor cells by CpG. Clin. Cancer Res., 2011, vol. 1, no. 17, pp. 1645-1648.
39. Leon S.A., Shapiro B., Sklaroff D.M., Yaros M.J. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res., 1977, vol. 37, no. 3, pp. 646-650.
40. Liu G., Zhao Y. Toll-like receptors and immune regulation: their direct and indirect modulation on regulatory CD4+ CD25+ T cells. Immunology, 2007, vol. 122, no. 2, pp. 149-156.
41. Magnusson M., Magnusson S., Vallin H., R nnblom L., Alm G.V. Importance of CpG dinucleotides in activation of natural IFN-alpha-producing cells by a lupus-related oligodeoxynucleotide. Scand. J. Immunol., 2001, vol. 54, no. 6, pp. 543-550.
42. Mandel P., Metais P. Les acides nucleiques du plasma sanguin chez l’homme. C. R. Acad. Sci. Paris, 1948, vol. 142, pp. 241-243.
43. Martinez-Martinez R.E., Abud-Mendoza C., Pati o-Marin N., Rizo-Rodr guez J.C., Little J.W., Loyola-Rodr guez J.P. Detection of periodontal bacterial DNA in serum and synovial fluid in refractory rheumatoid arthritispatients. J. Clin. Periodontol., 2009, vol. 36, no. 12, pp. 1004-1010.
44. Moseman E.A., Liang X., Dawson A.J., Panoskaltsis-Mortari A., Krieg A.M., Liu Y.J., Blazar B.R., Chen W. Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+ regulatory T cells. J. Immunol., 2004, vol. 1, no. 173, pp. 4433-4442.
45. Nagata S. Autoimmune diseases caused by defects in clearing dead cells and nuclei expelled from erythroid precursors. Immunol. Rev., 2007, vol. 220, pp. 237-250.
46. Pan W., Zhu S., Yuan M., Cui H., Wang L., Luo X., Li J., Zhou H., Tang Y., Shen N. MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J. Immunol., 2010, vol. 15, no. 184, pp. 6773-6781.
47. Pasare C., Medzhitov R. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science, 2003, vol. 14, no. 299, pp. 1033-1036.
48. Patole P.S., Anders H.J. Nucleic acids modulate autoimmunity through nucleic-acid-specific toll-like receptors. Curr. Med. Chem., 2006, vol. 13, no. 25, pp. 3061-3067.
49. Pawar R.D., Patole P.S., W rnle M., Anders H.J. Microbial nucleic acids pay a Toll in kidney disease. Am. J. Physiol. Renal Physiol., 2006, vol. 291, no. 3, pp. 509-516.
50. Peters D.L., Pretorius P.J. Origin, translocation and destination of extracellular occurring DNA – a new paradigm in genetic behavior. Clin. Chim. Acta, 2011, vol. 12, no. 412, pp. 806-811.
51. Philipp A.B., Stieber P., Nagel D., Neumann J., Spelsberg F., Jung A., Lamerz R., Herbst A., Kolligs F.T. Prognostic role of methylated free circulating DNA in colorectal cancer. Int. J. Cancer, 2012, vol. 15, no. 131, pp. 2308-2319.
52. Pisetsky D.S., Fairhurst A.M. The origin of extracellular DNA during the clearance of dead and dying cells. Autoimmunity, 2007, vol. 40, no. 4, pp. 281-284.
53. Rhodes A., Cecconi M. Cell-free DNA and outcome in sepsis. Crit. Care, 2012, vol. 8. no. 16, p. 170.
54. Richardson B.C., Strahler J.R., Pivirotto T.S., Quddus J., Bayliss G.E., Gross L.A., O’Rourke K.S., Powers D., Hanash S.M., Johnson M.A. Phenotypic and functional similarities between 5-azacytidine-treated T cells and a T cell subset in patients with active systemic lupus erythematosus. Arthritis Rheum., 1992, vol. 35, no. 6, pp. 647-662.
55. Richardson B.C., Yung R.L., Johnson K.J., Rowse P.E., Lalwani N.D. Monocyte apoptosis in patients with active lupus. Arthritis Rheum., 1996, vol. 39. no. 8, pp. 1432-1434.
56. Romagnani C., Chiesa D.M., Kohler S., Moewes B., Radbruch A., Moretta L., Moretta A., Thiel A. Activation of human NK cells by plasmacytoid dendritic cells and its modulation by CD4+ T helper cells and CD4+ CD25hi T regulatory cells. Eur. J. Immunol., 2005, vol. 35, no. 8, pp. 2452-2458.
57. Rothenfusser S., Hornung V., Krug A., Towarowski A., Krieg A.M., Endres S., Hartmann G. Distinct CpG oligonucleotide sequences activate human gamma delta T cells via interferon-alpha/-beta. Eur. J. Immunol., 2001, vol. 31, no. 12, pp. 3525-3534.
58. Rudin C.M., Thompson C.B. Apoptosis and disease: regulation and clinical relevance of programmed cell death. Annu Rev. Med., 1997, vol. 48, pp. 267-281.
59. Saukkonen K., Lakkisto P., Pettilä V., Varpula M., Karlsson S., Ruokonen E., Pulkki K.; Finnsepsis Study Group. Cell-free plasma DNA as a predictor of outcome in severe sepsis and septic shock. Clinical Chemistry, 2008, vol. 54, no. 6, pp. 1000-1007.
60. Skvortsova T.E., Vlassov V.V., Laktionov P.P. Binding and penetration of methylated DNA into primary and transformed human cells. Ann. N. Y. Acad. Sci., 2008, vol. 1137, pp. 36-40.
61. Sparwasser T., H ltner L., Koch E.S., Luz A., Lipford G.B., Wagner H. Immunostimulatory CpGoligodeoxynucleotides cause extramedullary murine hemopoiesis. J. Immunology, 1999, vol. 162, no. 4, pp. 2368-2374.
62. Stroun M., Anker P., Maurice P., Lyautey J., Lederrey C., Beljanski M. Neoplastic characteristics of the DNA found in the plasma of cancer patients. Oncology, 1989, vol. 46, no. 5, pp. 318-322.
63. Suzuki N., Kamataki A., Yamaki J., Homma Y. Characterization of circulating DNA in healthy human plasma. Clin Chim Acta, 2008, vol. 387. no. 1-2, pp. 55-58.
64. Swaminathan R., Butt A.N. Circulating nucleic acids in plasma and serum: recent developments. Ann. N. Y. Acad. Sci., 2006, vol. 1075, pp. 1-9.
65. Tan E.M., Schur P.H., Carr R.I., Kunkel H.G. Deoxyribonucleic Acid (DNA) and Antibodies to DNA in the Serum of Patients with Systemic Lupus Erythematosus. Journal of Clinical Investigation, 1966, vol. 45, no. 11, pp. 1732-1740.
66. Tang Q., Bluestone J.A. Regulatory T-cell physiology and application to treat autoimmunity. Immunol. Rev., 2006, vol. 212, pp. 217-237.
67. Umetani N., Giuliano A.E., Hiramatsu S.H., Amersi F., Nakagawa T., Martino S., Hoon D.S. Prediction of breast tumor progression by integrity of free circulating DNA in serum. J. of Clinical Oncology, 2006, vol. 24, no. 26, pp. 4270-4276.
68. Urry Z., Xystrakis E., Richards D.F., McDonald J., Sattar Z., Cousins D.J., Corrigan C.J., Hickman E., Brown Z., Hawrylowicz C.M. Ligation of TLR9 induced on human IL-10-secreting Tregs by 1alpha,25-dihydroxyvitamin D3 abrogates regulatory function. J. Clin. Invest., 2009, vol. 119, no. 2, pp. 387-398.
69. Weeratna R.D., Brazolot Millan C.L., McCluskie M.J., Davis H.L. CpG ODN can redirect the Th bias of established Th2 immune responses in adult and young mice. FEMS Immunol Med Microbiol., 2001, vol. 32. no. 1, pp. 65-71.
70. Wen Z.K., Xu W., Xu L., Cao Q.H., Wang Y., Chu Y.W., Xiong S.D. DNA hypomethylation is crucial for apoptotic DNA to induce systemic lupus erythematosus-like autoimmune disease in SLE-non-susceptible mice. Rheumatology (Oxford), 2007, vol. 46, no. 12, pp. 1796-1803.
71. Wong Ivy H.N., Dennis Lo Y.M., Lai Paul B.S. and Johnson Philip J. Relationship of p16 Methylation Status and Serum α-Fetoprotein Concentration in Hepatocellular Carcinoma Patients. Clinical Chemistry, 2000, vol. 46, no. 9, pp. 1420-1422.
72. Wong I.H., Lo Y.M., Johnson P.J. Epigenetic tumor markers in plasma and serum: biology and applications to molecular diagnosis and disease monitoring. Ann. N. Y. Acad. Sci., 2001, vol. 945, pp. 36-50.
73. Yasuda K., Richez C., Uccellini M.B., Richards R.J., Bonegio R.G., Akira S., Monestier M., Corley R.B., Viglianti G.A., Marshak-Rothstein A., Rifkin I.R. Requirement for DNA CpG content in TLR9-dependent dendritic cell activation induced by DNA-containing immune complexes. J. Immunol., 2009, vol. 1, no. 183, pp. 3109-3117.
74. Yoshinaga T., Yasuda K., Ogawa Y., Nishikawa M., Takakura Y. DNA and its cationic lipid complexes induce CpG motif-dependent activation of murine dendritic cells. Immunology, 2006, vol. 120, no. 3, pp. 295-302.
75. Yu M., Wan Y.F., Zou Q.H. Cell-free circulating mitochondrial DNA in the serum: a potential non-invasive biomarker for Ewing’s sarcoma. Arch. Med. Res., 2012, vol. 43, no. 5, pp. 389-394.
76. Yung R.L., Quddus J., Chrisp C.E., Johnson K.J., Richardson B.C. Mechanism of drug-induced lupus. I. Cloned Th2 cells modified with DNA methylation inhibitors in vitro cause autoimmunity in vivo. J. Immunology, 1995, vol. 154, no. 6, pp. 3025-3035.
77. Zhang R., Xing M., Ji X., Gu L., Yang X., Wang H., Jiang P. Interferon-alpha and interleukin-6 in SLE serum induce the differentiation and maturation of dendritic cells derived from CD34+ hematopoietic precursor cells. Cytokine, 2010, vol. 50, no. 2, pp. 195-203.
78. Zhong X.Y., von Mühlenen I., Li Y., Kang A., Gupta A.K., Tyndall A., Holzgreve W., Hahn S., Hasler P. Increased concentrations of antibody-bound circulatory cell-free DNA in rheumatoid arthritis. Clinical Chemistry, 2007, vol. 53, no. 9, pp. 1609-1614.
Для цитирования:
Козлов В.А. СВОБОДНАЯ ВНЕКЛЕТОЧНАЯ ДНК В НОРМЕ И ПРИ ПАТОЛОГИИ. Медицинская иммунология. 2013;15(5):399-412. https://doi.org/10.15789/1563-0625-2013-5-399-412
For citation:
Kozlov V.А. FREE EXTRACELLULAR DNA IN NORMAL STATE AND UNDER PATHOLOGICAL CONDITIONS. Medical Immunology (Russia). 2013;15(5):399-412. (In Russ.) https://doi.org/10.15789/1563-0625-2013-5-399-412
Просмотров: 1507
Послать статью по эл. почте 