ROLE OF PURINERGIC RECEPTORS IN IMMUNE RESPONSE

Cover Page


Cite item

Full Text

Abstract

Purine receptors are located on immune and somatic cells of animal and human organisms. Summation of signals from purine and TOLL-like receptors takes place on the level of inflammasome formation and results in summation of the first and second signals of innate immunity. The first signal - from PAMPs (pathogen associated molecular patterns), the second - from DAMPs (danger associated molecular patterns). Adenosine triphosphate (ATP) is the most studied DAMP. ATP connects with purine receptors, which include P2 (P2X7 receptors are the best described), that results in opening of channels of these receptors and transit of ATP into the cell. In parallel exit of K+ from cells and entrance of Ca2+ and Na+ into the cells is observed, that is associated with activation of the immune competent cell. Damaged cells dying via necrosis or apoptosis are the source of extracellular ATP, as well as activated immunocytes. Signals from P2 and TOLL-like receptors are summarized in effectors of immune response, and activation of P2 receptors in lymphocytes makes a contribution into activation of cells, mediated by T-cell receptor. Negative side of purine receptor activation is a stimulating effect on proliferation and metastasis of malignant cells. The practical output of knowledge on functioning of purine receptors for clinical immunology is the application of agonists and antagonists of purine receptors, as well as explanation of effect of immune modulators from the position of launch of K+/Na+-pump, resulting in prolonged activation of immune competent cells.

About the authors

I. B. Semenova

Mechnikov Research Institute of Vaccines and Sera

Author for correspondence.
Email: noemail@neicon.ru
Russian Federation

References

  1. Зиганшин А.У., Зиганшина Л.Е., Бернсток Дж. Р-2 рецепторы: теоретические предпосылки клинического воздействия. Бюллетень экспериментальной биологии и медицины. 2002, 134 (10): 365-370.
  2. Невская К.В., Огородова Л.М., Юрьева К.С.,Иванюк Е.Э.,Иккерт О.П. Салтыкова И.В., Сазонов А.Э. Особенности цитокинового профиля моноцитов при стимуляции аденозино-вых рецепторов in vitro. Цитокины и воспаление. 2014, 13 (1): 67-70.
  3. Серебряная Н.Б. Нуклеотиды как регуляторы иммунного ответа. Иммунология. 2010, 5: 273281.
  4. Серебряная Н.Б., Карпенко М.Н., Житнухин Ю.Л., Бисага Г.Н., Абдурасулова И.Н. Исследование протективного действия препарата ферровир при остром экспериментальном аллергическом энцефаломиелите. Цитокины и воспаление. 2010, 9 (1): 33-38.
  5. Bartlett R., Stokes L., Sluyter R. The P2X7 receptor channel: recent developments and the use of P2X7 antagonists in models of disease. Pharmacol Rev. 2014. Jul; 66 (3): 638-675.
  6. Bours M.J., Dagnelie PC., Giuliani A.L. et al. P2 receptors and extracellular ATP: a novel homeostatic pathway in inflammation. Front Biosci. 2011, Jun; 1 (3): 1443-1456.
  7. Bulanova E., Budagian V, Orinska Z. et al. Bulfone-Paus SATP induces P2X7 receptor-independent cytokine expression through P2X1 and P2X3 receptors in murine mast cells. J. Leukoc. Biol. 2009, Apr; 85 (4): 692-702.
  8. Castrichini M., Lazzerini PE., Gamberucci A. et al. The purinergic P2x7 receptor is expressed on monocytes in Behget's disease and is modulated by TNF-a. Eur. J. Immunol. 2014, Jan; 44 (1): 227238.
  9. Chen Q., Jin Y., Zhang K. et al. Alarmin HNP-1 promotes pyroptosis and IL-ф release through different roles of NLRP3 inflammasome via P2X7 in LPS-primed macrophages. Innate Immun. 2014, Apr; 20 (3): 290-300.
  10. Cisneros-Mejorado A., Perez-Samartin A., Gottlieb M., Matute C. ATP signaling in brain: release, excitotoxicity and potential therapeutic targets. Cell Mol. Neurobiol. 2015, Jan; 35 (1): 1-6.
  11. Coutinho-Silva R., Correa G., Sater A.A., Ojcius D.M. The P2X(7) receptor and intracellular pathogens: a continuing struggle. Purinergic Signal. 2009, Jun; 5 (2): 197-204.
  12. Di Virgilio F., Boeynaems J.M., Robson S.C. Extracellular nucleotides as negative modulators of immunity. Curr. Opin. Pharmacol. 2009, Aug; 9 (4): 507-513.
  13. Di Virgilio F., Bronte V., Collavo D., Zanovello P Responses of mouse lymphocytes to extracellular adenosine 5'-triphosphate (ATP). Lymphocytes with cytotoxic activity are resistant to the permeabilizing effects of ATP J. Immunol. 1989, Sep; 143 (6): 1955-1960.
  14. Dwyer K.M., Hanidziar D., Putheti P et al. Expression of CD39 by human peripheral blood CD4+ CD25+ T cells denotes a regulatory memory phenotype. Am. J. Transplant. 2010, Nov; 10 (11): 2410-2420.
  15. Ferrari D., La Sala A., Chiozzi P et al. The P2 purinergic receptors of human dendritic cells: identification and coupling to cytokine release. FASEB J. 2000, Dec; 14 (15): 2466-2476.
  16. Fredholm B.B., Abbracchio M.P, Burnstock G. et al. Nomenclature and classification of purino-ceptors. Pharmacol. Rev. 1994, Jun; 46 (2): 143-156.
  17. Gavala M.L., Liu YP, Lenertz L.Y. et al. Nucleotide receptor P2RX7 stimulation enhances LPS-induced interferon-P production in murine macrophages. J. Leukoc. Biol. 2013, Oct; 94 (4): 759768.
  18. Gebremeskel S., LeVatte T., Liwski R.S. et al. The reversible P2Y12 inhibitor ticagrelor inhibits metastasis and improves survival in mouse models of cancer. Int. J. Cancer. 2015, Jan; 136 (1): 234240.
  19. Ghiringhelli F., Apetoh L., Tesniere A. et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat. Med. 2009, Oct; 15 (10): 1170-1178.
  20. Gicquel T., Victoni T., Fautrel A. et al. Involvement of purinergic receptors and NOD-like receptor-family protein 3-inflammasome pathway in the adenosine triphosphate-induced cytokine release from macrophages. Clin. Exp. Pharmacol. Physiol. 2014, Apr; 41 (4): 279-286.
  21. Granstein R.D., Ding W, Huang J. et al. Augmentation of cutaneous immune responses by ATP gamma S: purinergic agonists define a novel class of immunologic adjuvants. J. Immunol. 2005, Jun 15; 174 (12): 7725-7731.
  22. Gu B.J., Rathsam C., Stokes L. et al. Extracellular ATP dissociates nonmuscle myosin from P2X(7) complex: this dissociation regulates P2X (7) pore formation. Am. J. Physiol. Cell Physiol. 2009, Aug; 297 (2): 430-439.
  23. Gu B.J., Saunders B.M., Jursik C., Wiley J.S. The P2X7-nonmuscle myosin membrane complex regulates phagocytosis of nonopsonized particles and bacteria by a pathway attenuated by extracellular ATP. Blood. 2010, Feb 25; 115 (8): 1621-1631.
  24. Gulinelli S., Salaro E., Vuerich M. et al. IL-18 associates to microvesicles shed from human macrophages by a LPS/TLR-4 independent mechanism in response to P2X receptor stimulation. Eur. J. Immunol. 2012, Dec; 42 (12): 3334-3345.
  25. Hasko G., Kuhel D.G., Salzman A.L., Szabo C. ATP suppression of interleukin-12 and tumour necrosis factor-alpha release from macrophages. Br. J. Pharmacol. 2000, Mar; 129 (5): 909-914.
  26. He Y., Franchi L., Nrnez G. TLR agonists stimulate Nlrp3-dependent IL-ф production independently of the purinergic P2X7 receptor in dendritic cells and in vivo. J. Immunol. 2013, Jan 1; 190 (1): 334-339.
  27. Hu Z., Murakami T., Suzuki K. et al. Antimicrobial cathelicidin peptide LL-37 inhibits the LPS/ ATP-induced pyroptosis of macrophages by dual mechanism. PLoS One. 2014, Jan 16; 9 (1): e85765.
  28. Idzko M., Dichmann S., Ferrari D. et al. Norgauer J. Nucleotides induce chemotaxis and actin polymerization in immature but not mature human dendritic cells via activation of pertussis toxin-sensitive P2y receptors. Blood. 2002, Aug 1; 100 (3): 925-932.
  29. Ikeda M., Tsuno S., Sugiyama T. et al. Ca(2+) spiking activity caused by the activation of store-operated Ca(2+) channels mediates TNF-a release from microglial cells under chronic purinergic stimulation. Biochim. Biophys. Acta. 2013, Dec; 1833 (12): 2573-2585.
  30. Janeway C.A., Jr. How the immune system protects the host from infection. Microbes Infect. 2001, Nov; 3 (13): 1167-1171.
  31. Koizumi S., Shigemoto-Mogami Y., Nasu-Tada K. et al. UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature. 2007, Apr 26; 446 (7139): 1091-1095.
  32. la Sala A., Ferrari D., Corinti S. et al. Extracellular ATP induces a distorted maturation of dendritic cells and inhibits their capacity to initiate Th1 responses. J. Immunol. 2001, Feb 1; 166 (3): 1611-1617.
  33. Loomis W.H., Namiki S., Ostrom R.S. et al. Hypertonic stress increases T cell interleukin-2 expression through a mechanism that involves ATP release, P2 receptor, and p38 MAPK activation. J. Biol. Chem. 2003, Feb 14; 278 (7): 4590-4596.
  34. Mandapathil M., Lang S., Gorelik E., Whiteside T.L. Isolation of functional human regulatory T cells (Treg) from the peripheral blood based on the CD39 expression J. Immunol. Methods. 2009, Jul 31; 346 (1-2): 55-63.
  35. Manohar M., Hirsh M.I., Chen Y et al. ATP release and autocrine signaling through P2X4 receptors regulate y8 T cell activation. J. Leukoc. Biol. 2012, Oct; 92 (4): 787-794.
  36. Michel A.D., Ng S.W, Roman S. et al. Mechanism of action of species-selective P2X(7) receptor antagonists. Br. J. Pharmacol. 2009, Apr; 156 (8): 1312-1325.
  37. Morandini A.C., Savio L.E., Coutinho-Silva R. The role of P2X7 receptor in infectious inflammatory diseases and the influence of ectonucleotidases. Biomed J. 2014, Aug; 37 (4): 169-177.
  38. Ousingsawat J., Wanitchakool P., Kmit A. et al. Anoctamin 6 mediates effects essential for innate immunity downstream of P2X7 receptors in macrophages. Nat. Commun. 2015, Feb 5; 6: 6245.
  39. Piccini A., Carta S., Tassi S. et al. ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1beta and IL-18 secretion in an autocrine way. Proc. Natl. Acad. Sci. USA. 2008, Jun 10; 105 (23): 8067-8072.
  40. Qiu F., Dahl G. A permeant regulating its permeation pore: inhibition of pannexin 1 channels by ATP. Am. J. Physiol. Cell Physiol. 2009, Feb; 296 (2): 250-255.
  41. Ralevic V, Burnstock G. Receptors for purines and pyrimidines. Pharmacol. Rev. 1998, Sep; 50 (3): 413-492.
  42. Rayah A., Kanellopoulos J.M., Di Virgilio F. P2 receptors and immunity. Microbes Infect. 2012, Nov; 14 (14): 1254-1262.
  43. Ren H., Teng Y, Tan B. et al. Toll-like receptor-triggered calcium mobilization protects mice against bacterial infection through extracellular ATP release. Infect. Immun. 2014, Dec; 82 (12): 50765085.
  44. Romio M., Reinbeck B., Bongardt S. et al. Extracellular purine metabolism and signaling of CD73-derived adenosine in murine Treg and Teff cells. Am. J. Physiol. Cell Physiol. 2011, Aug; 301 (2): 530-539.
  45. Schenk U., Frascoli M., Proietti M. et al. ATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors. Sci. Signal. 2011, Mar 1; 4 (162): ra12.
  46. Schenk U., Westendorf A.M., Radaelli E. et al. Purinergic control of T cell activation by ATP released through pannexin-1 hemichannels. Sci. Signal. 2008, Sep. 30; 1 (39): ra6.
  47. Schuler P.J., Harasymczuk M., Schilling B. et al. Separation of human CD4+CD39+ T cells by magnetic beads reveals two phenotypically and functionally different subsets. J. Immunol. Methods. 2011, Jun 30; 369 (1-2): 59-68.
  48. Shieh C.H., Heinrich A., Serchov T. et al. P2X7-dependent, but differentially regulated release of IL-6, CCL2, and TNF-a in cultured mouse microglia Glia. 2014, Apr; 62 (4): 592-607. doi:10.1002/ glia.22628. Epub 2014 Jan 28.
  49. Shoji K.F., Saez PJ., Harcha P.A. et al. Pannexin1 channels act downstream of P2X 7 receptors in ATP-induced murine T-cell death. Channels (Austin). 2014, 8 (2): 142-156.
  50. Sung S.S., Young J.D., Origlio A.M. et al. Extracellular ATP perturbs transmembrane ion fluxes, elevates cytosolic Ca2+, and inhibits phagocytosis in mouse macrophages. J. Immunol. 2001, Feb 1; 166 (3): 1611-1617.
  51. Vfelasquez S., Eugenin E.A. Role of Pannexin-1 hemichannels and purinergic receptors in the pathogenesis of human diseases. Front Physiol. 2014, Mar 14.
  52. Weber F.C., Esser P.R., Muller T. et al. Lack of the purinergic receptor P2X (7) results in resistance to contact hypersensitivity. J. Exp. Med. 2010, Nov 22; 207 (12): 2609-2619.
  53. Wiley J.S., Sluyter R., Gu B.J. et al. The human P2X7 receptor and its role in innate immunity. Tissue Antigens. 2011, Nov; 78 (5): 321-332.
  54. Xie R., Xu J., Wen G. et al. The P2Y2 nucleotide receptor mediates the proliferation and migration of human hepatocellular carcinoma cells induced by ATP. J. Biol. Chem. 2014, Jul 4; 289 (27): 19137-19149.
  55. Yao Y., Levings M.K., Steiner T.S. ATP conditions intestinal epithelial cells to an inflammatory state that promotes components of DC maturation. Eur. J. Immunol. 2012, Dec; 42 (12): 33103321.
  56. Yip L., Woehrle T., Corriden R. et al. Autocrine regulation of T-cell activation by ATP release and P2X7 receptors. FASEB J. 2009, Jun; 23 (6): 1685-1693.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2016 Semenova I.B.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС77-75442 от 01.04.2019 г.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies