ГУМОРАЛЬНЫЙ И КЛЕТОЧНЫЙ ИММУНИТЕТ ПРОТИВ АТЕРОСКЛЕРОЗА: ВОЗМОЖНОСТЬ СОЗДАНИЯ ВАКЦИНЫ


Цитировать

Полный текст

Аннотация

Развитие атеросклероза находится под влиянием врожденного и приобретенного иммунитета. Врожденный иммунный ответ совершается макрофагами, дендритными клетками, экспрессирующими на поверхностной мембране клеток скэвенджер- и Toll-подобные рецепторы, а также естественные антитела, способные распознавать белки, липиды, нуклеиновые кислоты, углеводы. Т- и В-лимфоциты с помощью антигенных рецепторов могут также, но с большей специфичностью, участвовать в распознавании молекул, в том числе наиболее важных в атеросклерозе. Имеются наблюдения, предполагающие, что селективная супрессия проатерогенных или селективная активация антиатерогенных иммунных ответов может обеспечить новые подходы для предотвращения или лечения атеросклероза.

Об авторах

В А НАГОРНЕВ

ГУ «Научно-исследовательский институт экспериментальной медицины РАМН»; ГНЦ «Государственный научно-исследовательский институт особо чистых биопрепаратов ФМБА России», Санкт-Петербург

Академик РАМН

С А КЕТЛИНСКИЙ

ГУ «Научно-исследовательский институт экспериментальной медицины РАМН»; ГНЦ «Государственный научно-исследовательский институт особо чистых биопрепаратов ФМБА России», Санкт-Петербург

член-корреспондент РАМН

Список литературы

  1. Аничков Н. Н. Главные результаты исследований, проведенных в отделе патологической анатомии Института экспериментальной медицины АМН СССР//Вестн. АМН СССР. 1961. № 11. С. 33-40.
  2. Денисенко А. Д., Виноградов А. Г., Нагорнев В. А. и др. Взаимодействие макрофагов с
  3. Климов А. Н. Аутоиммунная теория атерогенеза и концепция модифицированных липопротеидов // Вести. АМН СССР. 1990. № 11. С. 30-36.
  4. Климов А. Н., Нагорнев В А., Денисенко А. Д. Изучение иммунологических механизмов развития атеросклероза и новые методы его диагностики и лечения // Мед. акад. журн. 2005. Т. 5. № 2. С. 18-32.
  5. Нагорнев В. А. Патогенез атеросклероза. 2007.
  6. Ait-Oufella Н., Salomon B.L., Potteaux S. et al. Natural regulatory T cells control the development of atherosclerosis in mice // Nat. Med. 2006. Vol. 12. P. 178-180.
  7. Ameli S., Hultgardh-Nilsson S., Regnstrom J. et al. Effect of immunization with homologous LDL and oxidized LDL on early atherosclerosis in hypercholesterolemic rabbits // Arterioscler. Thromb. Vase. Biol. 1996. Vol. 16. P. 1074-1079.
  8. Alipour A., van Oostrom J.H.H.M., Israeljan A. et al. Leukocyte activation by triglyceride-rich lipoproteins //Ateroscler. Thromb. Vase. Biol. 2008. Vol. 28. P. 792-797.
  9. Anitshkov N. Uber die Veranderungen der Kaninchen aorta bei experimenteller Cholesterin-steatose // Beitrag. pathol. Anat. und allgem. Pathol. 1913. Bd. 56. S. 379-405.
  10. Baum PR., Gayle B.B., Ramsdell. Molecular characterization of murine aqnd human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1 regulated protein gp34 // Embo J. 1994. Vol. 13. P. 3992-4001.
  11. Benko S., Magyarics Z., Szabo A. et al. Dendritic cell subtypes as primary targets of vaccines: the emerging role and cross-talk of pattern recognition receptors // Biol. Chem. 2008. Vol. 389. P. 469-485.
  12. Bettelli E., Oukka, Kuchroo. T(H)-17 cells in the circle of immunity and autoimmunity // Nat. Immunol. 2007. Vol. 8. P. 345-350.
  13. Blankenberg S., Tirel L., Bickel C. Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina // Circulation. 2002. Vol. 106. P. 24-30.
  14. Bochkov V. N., Mechtcheriakova D., Lucerna M. et al. Oxidized phospholipids stimulate tissue factor expression in human endothelial cells via activation of ERK/ EGR-1 and Ca(++0 NFAT // Blood. 2002. Vol. 99. P. 199-206.
  15. Buono C. et al. T-bet deficiency reduces atherosclerosis and alters plaque antigen-specific immune responses // Proc. Natl. Acad. Sci. USA. 2005. Vol. 102. P. 15961601.
  16. Caligiuri G., Nicoletti A., Poirier В., Hansson G. K. Protective immunity carried by В cells of hypercholesterolemic mice // J. Clin. Invast. 2002. Vol. 109. P. 745-753.
  17. Chen Z., Tato L., Muul A. et al. Distinct regulation of interleukin-17 in human T-helper lymphocytes // Arthritis Rheum. 2007. Vol. 56. P. 2936-2946.
  18. Cheng X., Liao H., Ge B. Thl/Th2 functional imbalance after acute myocardial infarction: coronary arterial inflammation of myocardial inflammation or myocardial inflammation // J. Clin. Immunol. 2005. Vol. 25. P. 246-253.
  19. Cheng X, Yu X., Ying-jan Ding et al. The Thl7/Treg imbalance in patients with acute coronary syndrome // Clin. Immunol. 2008. Vol. 127. P. 89-97.
  20. Choi J., Enis D. R., Koh K. P. et al. T lymphocyte-endothelial cell interactions // Annu. Rev. Immunol. 2004. Vol. 22. P. 683-709.
  21. Csiszar A., Ungravi Z. Sinergistic effects of vascular IL-17 and TNF-a may promote coronary artery disease // Med. Hypotheses. 2004. Vol. 63. P. 696-698.
  22. Cui M. Z., Perm M. S., Chisolm G. M. Native and oxidized low density lipoprotein induction of tissue factor gene expression in smooth muscle cells is mediated by both Egr-1 and Spt // J. Biol. Chem. 1999. Vol. 274. P. 32795-32802.
  23. Edfeldt K., Swedeborg J., Hansson G.K., Yan Z-Q. Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation // Circulation. 2002. Vol. 105. P. 1158-1161.
  24. Elhage R., Courdy P., Brouchet L. et al. Deleting TCRccP or CD4+ T cells leads to opposite effects on site-specific atherosclerosis in famalt ApoE '' deficient mice //Am. J. Pathol. 2004. Vol. 165. P. 2013-2018.
  25. Faure E., Thomas L., Xu H. et al. Bacterial lipopoly-saccharide and IFN-y induce Toll-like receptor 2 and Toll-like Receptor 4 expression in human endothelial cells: role NF-кВ activation // J. Immunol. 2001. Vol. 166. P. 2018-2024.
  26. Fong L.G., Albert T.S., Horn S.E. Inhibition of the mac-rophages-induced oxidation of LDL by interferon-gam-ma // J. Lipid. Res. 1994. Vol. 35. P. 893-904.
  27. Fredrikson G.K., Hedblad В., Berglund G. et al. Identification of immune responses against aldehydemodified peptide sequences in apo B-100 associated with cardiovascular disease // Arterioscler. Thromb. Vase. Biol. 2003. Vol. 23. P. 872-878.
  28. Fredrikson G.K., Andersson L., Soderberg I. et al. Atheroprotective immunization with MDA-modified apoB-100 peptide sequences is associated with activation of Th2 specific antibody expression //Autoimmunity. 2005. Vol. 38. P. 171-179.
  29. Fredrikson G.K., Hedblad В., Berglund G. et al. Association between IgM against an aldehyde-modified peptide in Apolipoprotein B-100 and progression of carotid disease // Stroke. 2007. Vol. 38. P. 1495-1500.
  30. Fredrikson G. K., Bjorkhacka H., Soderberg I. Treatment with apoB peptide vaccines inhibits atherosclerosis in human apoB-100 transgenic mice without inducing an increase in peptide-specific antibodies // J. Intern. Med. 2008. Vol. 10. P. 1-8.
  31. Frostegard J., Ulfgren A. K., Nyberg P. et al. Cytokine expression in advanced human atherosclerotic plaques: dominance of proinflammatory (Thl) and macrophage-stimulating cytokines // Atherosclerosis. 1999. Vol. 145. P. 33-43.
  32. Gejrge J., Afek A., Gilburd B. Hyperimmunization of ApoE deficient mice with homologous malondialdegid low-density lipoprotein suppresses early atherogenesis //Atherosclerosis. 1998. Vol. 138. P. 147-152.
  33. George J. et al. Supression of early atherosclerosis in LDL-receptor deficient mice by oral tolerance with P2-glycoprotein 1 // Cardiovasc. Res. 2004. Vol. 62. P. 603-609.
  34. Gong J., Koido S., Calderwood S.K. Cell fusion: from hybridoma to dendritic cell-based vaccine // Expert. Rev. Vaccines. 2008. Vol. 7. P. 1055-1068.
  35. Hansson G. K. Vaccination against atherosclerosis. Science of fiction? // Circulation. 2002. Vol. 106. P. 337356.
  36. Hansson G. K. Inflammation, atherosclerosis, and coronary disease //N. Engl. J. Med. 2005. Vol. 352. P. 1685-1695.
  37. Hansson G. K. Atherosclerosis - an immune disease. The Anitschkov lecture 2007 //Atherosclerosis. 2009. Vol. 202. P. 2-10.
  38. Hansson G. K., Libby P. The immune response in atherosclerosis: a double-edged sword // Nature Rev. Immunol. 2006. Vol. 6. P. 508-519.
  39. Harats D., Yacov N., Gilburn B. Oral tolerance with heat shock protein-65 attenuates Mycobacterium tuberculosis-induced and high-fat-diet-driven atherosclerotic lesions // J. Am. Coll. Cardiol. 2002. Vol. 40. P. 1333-1338.
  40. Hashmi S., Zeng Q. T. Role of interleukin-17 and interleukin-17 - induced cytokines interleukin-6, interleukin-8 in unstable coronary artery disease // Artery Dis. 2006. Vol. 17. P. 699-706.
  41. Hauer A. D., Uyttenhove C, de Vos P. et al. Blocade of interleukin-12 function by protein vaccination attenuates atherosclerosis // Circulation. 2005. Vol. 112. P. 1054-1062.
  42. Hendersen E. L. et al. Death of smooth muscle cells and expression of mediators of apoptosis by T cells in aorta aneurysms // Circulation. 1999. Vol. 99. P. 96-104.
  43. Horkko S., Miller E. et al. Immunization of LDL receptor-deficient mice with homologous malandialde-hyde-modified and native LDL reduces progression of atherosclerosis by mechanisms other than induction of high titers of antibodies to oxidative neoepitopes // Arterioscler. Thromb. Vase. Biol. 1998. Vol. 18. P. 19721982.
  44. Horkko S., Binder C. J., Shaw P. X. et al. Immunological responses to oxidized LDL // Free Radic. Biol. Med. 2000. Vol. 28. P. 1771-1779.
  45. Huber S.A., Sakkinen P, David C, Chen C, Tracy R.P. T helper cells phenotype regulates atherosclerosis in mice under conditions of mild hypercholesterjlemia // Circulation. 2001. Vol. 103. P. 2610-2616.
  46. Imura A., Hori Т., Ishikawa T. et al. The human ОХ40/ gp34 system directly mediates adhesion of activated T cells to vascular endothelial cells // J. Exp. Med. 1996. Vol. 183. P. 2185-2195.
  47. Ito Т., Wang Y. H., Duramad O. et al. OX40 ligand shuts down IL-10-producing regulatory T cells // Proc. Natl. Acad. Sci. USA. 2006. Vol. 103. P. 1313813143.
  48. Kolls J.K., Linden A. Interleukin-17 family members and inflammation // Immunity. 2004. Vol. 21. P. 467-176.
  49. Li H., Sun B. Toll-like receptor 4 in atherosclerosis // J. Cell. Mol. Med. 2007. Vol. 11. P. 88-95.
  50. Libby P. Inflammation in atherosclerosis // Nature. 2002. Vol. 420. P. 868-874.
  51. Liu-Wu Y, Hurt-Camejo E., Wiklund O. Lysophos-phatidylcholine induces the production of IL-1 beta by human monocytes //Atherosclerosis. 1998. Vol. 137. P. 351-357.
  52. Lotze M.T., Thomson A.W. Dendritic cells: Biology and Clinical Applications. 2nd edition. San Diego, CA: Academic Press, 2001.
  53. Lutgens E., Cleutjens К. В., Heeneman S. et al. Both early and delayed anti-CD40L antibody treatment induces a stable plaque phenotype // Proc. Natl. Acad. Sci. USA. 2000. Vol. 97. P. 7464-7469.
  54. Madan M. and Amar S. Toll-like receptor-2 mediates diet and/or pathogen assocated atherosclerosis: proteomic findings // Plos. One. 2008. Vol. 3. P. 1-12.
  55. Mallat Z. et al. Protective role of IL-10 in atherosclerosis // Circ. Res. 1999. Vol. 85. P. 17-24.
  56. Mallat Z., Gojova A., Brun V. et al. Induction of a regulatory T-cell type 1 response reduces the development of atherosclerosis in apolipoprotein E-knockout mice //2003. Vol. 108. P. 1232-1237.
  57. Malmstrom V, Shiplon D., Singh B. CD134L expression on dendritic cells in the mesenteric lypmph nodes drives colitis in T cell-restored SCID mice // J. Immunol. 2001. Vol. 166. P. 6972-6981.
  58. Mangan M.E., Flierman L.M., van Duivenvoord H.J. et al. Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells // Arthritis. Rheum. 2005. Vol. 52. P. 2212-2221.
  59. Maron R., Sukhova G., Faria A.M. et al. Mucosal administration of heat shock protein-65 decreases atherosclerosis and inflammation in aorta arch of low-density lipoprotein receptor-deficient mice // Circulation. 2002. Vol. 106. P. 1708-1715.
  60. McLaren J.E., Ramji D. Interferon gamma : a master regulator of atherosclerosis // Cytokine & Growth factor reviews. 2009. Vol. 20. P. 125-135.
  61. Medhitov R. Toll-like receptors and innate immunity //Nat. Rev. Immunol. 2006. Vol. 1. P. 135-145.
  62. Melief C. J. Cancer immunotherapy by dendritic cells // Immunity. 2008. Vol. 29. P. 372-383.
  63. Methe H., Brunner S., Wiegand D. Enhanced T-helper-1 lymphocyte activation patterns in acute coco-nary syndromes // J. Am. Coll. Cardiol. 2005. Vol. 45. P. 1939-1945.
  64. Moore K.J., Freeman M.W. Scavanger receptors in atherosclerosis: beyond lipid uptake // Arterioscler. Tromb. Vase. Biol. 2006. Vol. 26. P. 208-222.
  65. Nilsson J., Hansson J. K., Shah P. K. Immunomodulation of atherosclerosis. Implications for vaccine development // Arterioscler. Thromb. Vase. Biol. 2005. Vol. 25. P. 18-28.
  66. Okabe Т., Kishimoto C, Shimada K. et al. Effects of late administration of immunoglobulin on experimental atherosclerosis in apolipoprotein E-deficient mice // Exp. Invest. 2005. Vol. 69. P. 1543-1546.
  67. Palinski W., Miller E., Witztum J.L. Immunization of low density lipoprotein (LDL) receptor-deficient rabbits with homologous malondialdehyde-modified LDL reduces atherogenesis // Proc. Natl. Acad. Sci. USA. 1995. Vol. 92. P. 821-825.
  68. Podrez E.A., Shmitt D., Hoff H.F. et al. Myeloperoxidase-generated nitrogen species convert LDL into an atherogenic form in vitro // J. Clin. Invest. 1999. Vol. 103. P. 1547-1560.
  69. Reyes O. S., Chyu K. Y., Yano J. et al. Immunization with a novel human Apo B-100 related peptide reduces atherosclerosis and inflammation in apo E null mice // 2002. Vol. 39 (Suppl. A). S. 240A.
  70. Robertson A.K.L., Rudling M., Zhou X. et al. Disruption of TGF-P signaling in T cells accelerates atherosclerosis // J. Clin. Invest. 2003. Vol. 112. P. 13421350.
  71. Roselaar S.E., Kakkanathu P.X., Daugherry A. Lymphocyte population in aterosclerosis lesions of ApoE"'" and LDLR '" mice. Decreasing density with disease progression // Arterioscler. Tromb. Vase. Biol. 1996. Vol. 16. P. 1013-1018.
  72. Roselaar S.E., Daugherry A. ApoE deficient mice have impaired innate response to Listeria monocytogenes in vivo // J. Lipid. Res. 1999. Vol. 40. P. 680-685.
  73. Sainz J., Sata M. Open Seasame! CXCR4 blockade recruits neutrophils into the plaque // Circ. Res. 2008. Vol. 102. P. 154-156.
  74. Sakaguchi S., Ono R., Setoguchi H. Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tol-eranc and autoimmu disease // Immunol. Rev. 2006. Vol. 212. P. 8-27.
  75. Sasu S., LaVerda D., Qureshi N. Clamidia pneumonia and Clamidial heat shock protein 60 stimulate proliferation of human vascular smooth muscle cells via toll-like receptor 4 b p44/42 mitogen-activated protein kinase activation // Circ. Res. 2001. Vol. 89. P. 244-250.
  76. Al-Shamkhani A., Birkeland M.L., Puklavec M. et al. CD40 is differentially expressed on activated rat and mouse T cells and is the sole receptor for the OX40 ligand // Eur. J. Immunol. 1996. Vol. 26. P. 1695-1699.
  77. Schiopu A., Bengtsson J., Soderberg I. et al. Recombinant human antibodies against aldehydemodified apolipoprotein B-100 peptide sequences inhibit atherosclerosis // Circulation. 2004. Vol. 102. P. 2919-2922.
  78. Schiopu A., Frendeus В., Jansson B. et al. Recombinant antibodies to an oxidized lowOdensity lipoprotein epitope ind rapid regression of atherosclerosis in apobec-1"'" low density lipoprotein idyreceptor'- mice // J. Am. College Cardiol. 2008. Vol. 50. P. 23132318.
  79. Schonbeck U., Libby P. The CD40/CD154 receptor/ligand dyad // Cell. Mol. Life. Sci. 2001. Vol. 58. P. 4-43.
  80. Schoneveld O.N., van M. Laman de K. et al. Tolllike receptor 2 stimulation induces intimal hyperplasia and atherosclerrotic lesion development // Cardiovasc. Res. 2005. Vol. 66. P. 162-169.
  81. Sjogren P., Fredrikson G.N., Samnegard A. et al. High plasma concentration of autoantibodies against native peptide 210 of apo B-100 are related to less coronary atherosclerosis and lower risk of myocardial infarction // Eur. Heart J. 2008. Vol. 29. № 18. P. 2218-2226.
  82. Swirski F.K., Pittet M.J., Kircher M.F. et al. Monocyte accumulation in mouse atherogenesis is progressive and propotional to extent of disease // Proc. Natl. Acad. Sci. USA. 2006. Vol.103. P. 1340-1345.
  83. Taleb S., Tegui A., Mallat Z. Regulatory T cell immunity and its relevance to atherosclerosis // J. Intern. Med. 2008. Vol. 263. P. 489-499.
  84. Takahara N., Kashiwag A., Maegawa H. et al. Lisophosphatidylcholine stimulated the expression and production of MCP-1 by human vascular endothelial cells // Metabolism. 1996. Vol. 45. P. 59-64.
  85. Takeda К., Akira S. Microbial recognition by Tolllike receptors // J. Dermatol. Sci. 2004. Vol. 34. P. 73-82.
  86. Tellides G. Interferon-y elicits atherosclerosis in the ad-sence of leucocytes // Nature. 2000. Vol. 403. P. 207211.
  87. Tornvall P., Waeg G., Nilsson J. et al. Autoantibodies against modified low-density lipoproteins in coronary artery disease // Atherosclerosis. 2003. Vol. 167. P. 347-353.
  88. Tupin E., Nicoletti A., Eihage R. et al. CDl-dependent activation of NKT cell aggravates atherosclerosis // J. Exp. Med. 2004. Vol. 199. P. 417-422.
  89. Eva J.A. van Wanrooij, Gijs H.M., van Puijvelde et al. Interruption of the Tnfrsf4/Tnfsf4 (OX40/OX40L0) pathway attenuates atherogenesis in low-density lipoprotein receptor-deficient mice //Arterioscler. Thromb. Vase. Biol. 2007. Vol. 27. P. 204-210.
  90. Weber C, Zeraecke A. and Libby P. The multifaceted contridutionjf leukocyte subset to aterosclerosis: lessons from mouse models // Nature Rev. Immunol. 2006. Vol. 8. P. 802-815.
  91. Wilson N. J., Boniface K., Chan B.S. et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells // Nat. Immunol. 2007. Vol. 8. P. 950-957.
  92. Xu X.H., Shah P.K., Faure E. et al. TLR-4 is expressed by macrophages in murine and human lipid-rich atherosclerotic plaques and upregulated by oxidized LDL // Circulation. 2001. Vol. 104. P. 3103-3108.
  93. Zernecke A., Bot I., Djalali-Talab Y. et al. Protective role of CXCR4/CXCL12 unveils the importance of neutrophils in atherosclerosis // Circ. Res. 2008. Vol. 102. P. 154-156.
  94. Zhou X., Stemme S., Hansson G.K. Evidence for a local immune response in atherosclerosis. CD4+ T cells infiltrate lesions of apoprotein - E-defi-cient mice //Am. J. Pathol. 1996. Vol. 149. P. 359366.
  95. Zhou X., Nicoletti A., Eihage R., Hansson G.K. Transfer of CD4+ T cells aggravates atherosclerosis in im-munodeficient apolipoprotein E knockout mice // Circulation. 2000. Vol. 102. P. 2919-2922.

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML
Скачать

© НАГОРНЕВ В.А., КЕТЛИНСКИЙ С.А., 2009

Creative Commons License
Эта статья доступна по лицензии Creative Commons Attribution 4.0 International License.

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).