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Molecular mechanisms for regulation of the functional activity of blood cells: improvement of targeted anti-inflammatory therapy

DOI: https://doi.org/10.29296/25877305-2019-11-03
Issue: 
11
Year: 
2019

Professor V. Barinov(1), MD; Kh. Grigoryan(2), Candidate of Medical Sciences; T. Faber(1); V. Sokhina(1); A. Perenesenko(1) 1-M.Gorky Donetsk National Medical University, Ukraine 2-Donetsk Regional Clinical Territorial Medical Association, Ukraine

The frequency of complications associated with the development of acute inflammation and recurrent chronic diseases necessitates the improvement of conventional methods for prevention and treatment. The promising area in the development of targeted therapy is the management of the mechanisms for leukocyte activation and recruitment from circulating blood into the focus of inflammation, which would bring us closer to the possibility of controlled development of the inflammatory response. The review provides much evidence for modulation of the functional activity of leukocytes and their transendothelial migration during stimulation of α- and β-adrenergic receptors. It discusses the practical significance of the leukocyte expression of purinergic P2 receptors. The review also presents the possible mechanisms for activation of monocytes and macrophages during stimulation of P2X receptors (P2X1, P2X4, P2X5, and P2X7), which makes it possible to predict their anti-inflammatory potential, as well as to control the development of inflammation in future. It analyzes the regulatory capabilities of the main subtypes of P2Y receptors (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14), which are involved in the regulation of phagocytosis, the secretion of cytokines, and the adhesion and migration of leukocytes. The authors consider the role of platelets that express purine receptors (P2Y1, P2Y12, P2Y14, and P2X1) in the recruitment and chemotaxis of leukocytes in inflammation and provide evidence that there are prospects for the selective action on blood cell adrenergic and purinergic receptors as a therapeutic target in a systemic inflammatory response.

Keywords: 
therapy
inflammation
leukocytes
platelets
α- and β-adrenergic receptors
purine P2 receptors



References: 
  1. Scanzano A/, Cosentino M. Adrenergic regulation of innate immunity: a review // Front Pharmacol. – 2015; 6: 171. DOI: 10.3389/fphar.2015.00171.
  2. Vasamsetti S., Florentin J., Coppin E. et al. Sympathetic Neuronal Activation Triggers Myeloid Progenitor Proliferation and Differentiation // Immunity. – 2018; 49 (1): 93–106.e7. DOI: 10.1016/j.immuni.2018.05.004.
  3. Kalkoff M., Chan-Dominy A., Sleigh J. et al. Alpha1-adrenergic receptor mRNA and inflammatory mediator expression in circulating leucocytes after cardiac surgery // Anaesth Intensive Care. – 2008; 36 (4): 535–43. DOI: 10.1177/0310057X0803600406.
  4. Bai A., Lu N., Guo Y. et al . Modulation of inflammatory response via alpha2-adrenoceptor blockade in acute murine colitis // Clin Exp Immunol. – 2009; 156 (2): 353–62. DOI: 10.1111/j.1365-2249.2009.03894.x.
  5. da Silva Rossato J., Krause M., Fernandes A. et al. Role of alpha- and beta-adrenoreceptors in rat monocyte/macrophage function at rest and acute exercise // J. Physiol. Biochem. – 2014; 70 (2): 363–74. DOI: 10.1007/s13105-013-0310-3.
  6. Sud R., Spengler R., Nader N. et al. Antinociception occurs with a reversal in alpha 2-adrenoceptor regulation of TNF production by peripheral monocytes/macrophages from pro- to anti-inflammatory // Eur. J. Pharmacol. – 2008; 588 (2–3): 217–31. DOI: 10.1016/j.ejphar.2008.04.043.
  7. Horn N., Anastase D., Hecker K. et al. Epinephrine enhances platelet-neutrophil adhesion in whole blood in vitro // Anesth. Analg. – 2005; 100 (2): 520–6. DOI: 10.1213/01.ANE.0000141527.60441.B7.
  8. Chigaev A., Waller A., Amit O. et al. Galphas-coupled receptor signaling actively down-regulates alpha4beta1-integrin affinity: a possible mechanism for cell de-adhesion // BMC Immunol. – 2008; 9: 26. DOI: 10.1186/1471-2172-9-26.
  9. Laudanna C., Campbell J., Butcher E. Elevation of intracellular cAMP inhibits RhoA activation and integrin-dependent leukocyteadhesion induced by chemoattractants // J. Biol. Chem. – 1997; 272 (39): 24141–4.
  10. Herrera-Garcia A., Dominguez-Luis M., Arce-Franco M. et al. Prevention of neutrophil extravasation by β2-adrenoceptor-mediated endothelial stabilization // J. Immunol. – 2014; 193 (6): 3023–35. DOI: 10.4049/jimmunol.1400255.
  11. Grisanti L., Gumpert A., Traynham C. et al. Leukocyte-expressed β2-adrenergic receptors are essential for survival after acute myocardial injury // Circulation. – 2016; 134 (2): 153–67. DOI: 10.1161/CIRCULATIONAHA.116.022304.
  12. Roca R., Esteban P., Zapater P. β2 adrenergic receptor functionality and genotype in two different models of chronic inflam-matory disease: Liver cirrhosis and osteoarthritis // Mol. Med. Rep. – 2018; 17 (6): 7987–95. DOI: 10.3892/mmr.2018.8820.
  13. Mueller H., Motulsky H., Sklar L. The potency and kinetics of the β-adrenergic receptors on human neutrophils // Mol. Pharmacol. – 1988; 34 (3): 347–53.
  14. Saygin D., Wanner N., Rose J. et al. Relative quantification of beta-adrenergic receptor in peripheral blood cells using flow cytometry // Cytometry A. – 2018; 93 (5): 563–70. DOI: 10.1002/cyto.a.23358.
  15. Landmann R. Beta-adrenergic receptors in human leukocyte subpopulations // Eur. J. Clin. Invest. – 1992; 22 (1): 30–6.
  16. Silvestri M., Oddera S., Lantero S. et al. beta 2-agonist-induced inhibition of neutrophil chemotaxis is not associated with modification of LFA-1 and Mac-1 expression or with impairment of polymorphonuclear leukocyte antibacterial activity // Respir. Med. – 1999; 93 (6): 416–23.
  17. Wahle M., Greulich T., Baerwald C. et al. Influence of catecholamines on cytokine production and expression of adhesion molecules of human neutrophils in vitro // Immunobiology. – 2005; 210 (1): 43–52. DOI: 10.1016/j.imbio.2005.02.004
  18. Brunskole H., Reinartz M., Kälble S. Dissociations in the effects of β2-adrenergic receptor agonists on cAMP formation and superoxide production in human neutrophils: support for the concept of functional selectivity // PLoS One. – 2013; 8 (5): e64556. DOI: 10.1371/journal.pone.0064556.
  19. Marino F., Scanzano A., Pulze L. β2-Adrenoceptors inhibit neutrophil extracellular traps in human polymorphonuclear leukocytes // J. Leukoc. Biol. – 2018; 104 (3): 603–14. DOI: 10.1002/JLB.3A1017-398RR.
  20. Hinchado M., Giraldo E., Ortega E. Adrenoreceptors are involved in the stimulation of neutrophils by exercise-induced circulating concentrations of Hsp72: cAMP as a potential «intracellular danger signal» // J. Cell Physiol. – 2012; 227 (2): 604–8. DOI: 10.1002/jcp.22759.
  21. Suurväli J., Boudinot P., Kanellopoulos J. et al. R2H4: A fast and sensitive purinergic receptor // Biomed. J. – 2017; 40 (5): 245–56. DOI: 10.1016/j.bj.2017.06.010.
  22. Layhadi J., Fountain S. R2H4 receptor-dependent Ca2+ influx in model human monocytes and macrophages // Int. J. Mol. Sci. – 2017; 18 (11): E2261. DOI: 10.3390/ijms18112261.
  23. Huang P., Zou Y., Zhong X. et al. R2H4 forms functional ATP-activated cation channels on lysosomal membranes regulated by luminal pH // J. Biol. Chem. – 2014; 289 (25): 17658–67. DOI: 10.1074/jbc.M114.552158.
  24. Campwala H., Fountain S. Constitutive and agonist stimulated ATP secretion in leukocytes // Commun. Integr. Biol. – 2013; 6 (3): e23631. DOI: 10.4161/cib.23631.
  25. Hiller S., Heldmann S., Richter K. et al. β-Nicotinamide adenine dinucleotide (β-nad) inhibits atp-dependent il-1β release from human monocytic cells // Int. J. Mol. Sci. – 2018; 19 (4): E1126. DOI: 10.3390/ijms19041126.
  26. Erb L., Weisman G. Coupling of R2Y receptors to G proteins and other signaling pathways // Wiley Interdiscip. Rev. Membr. Transp. Signal. – 2012; 1 (6): 789–803. DOI:10.1002/wmts.62.
  27. von Kügelgen I., Hoffmann K. Pharmacology and structure of R2Y receptors // Neuropharmacology. – 2016; 104: 50–61. DOI: 10.1016/j.neuropharm.2015.10.030.
  28. Le Duc D., Schulz A., Lede V. et al. R2Y Receptors in Immune Response and Inflammation // Adv. Immunol. – 2017; 136: 85–121. DOI: 10.1016/bs.ai.2017.05.006.
  29. De Ita M., Vargas M., Carbajal V. et al. ATP releases ATP or other nucleotides from human peripheral blood leukocytes through purinergic P2 receptors // Life Sci. – 2016; 145: 85–92. DOI: 10.1016/j.lfs.2015.12.013.
  30. Oliveira S., Oliveira N., Meyer-Fernandes J. et al. Increased expression of NTPDases 2 and 3 in mesenteric endothelial cells during schistosomiasis favors leukocyte adhesion through R2Y1 receptors // Vascul. Pharmacol. – 2016; 82: 66–72. DOI: 10.1016/j.vph.2016.02.005.
  31. Riegel A., Faigle M., Zug S. et al. Selective induction of endothelial R2Y6 nucleotide receptor promotes vascular inflammation // Blood. – 2011; 117 (8): 2548–55. DOI: 10.1182/blood-2010-10-313957.
  32. Nishimura A., Sunggip C., Oda S. Purinergic R2Y receptors: Molecular diversity and implications for treatment of cardiovascular diseases // Pharmacol. Ther. – 2017; 180: 113–28. DOI: 10.1016/j.pharmthera.2017.06.010.
  33. Amison R., Momi S., Morris A. et al. RhoA signaling through platelet R2Y receptor controls leukocyte recruitment in allergic mice // J. Allergy Clin. Immunol. – 2015; 135 (2): 528–38. DOI: 10.1016/j.jaci.2014.09.032.
  34. Amison R., Arnold S., O’Shaughnessy B. et al. Lipopolysaccharide (LPS) induced pulmonary neutrophil recruitment and platelet activation is mediated via the R2Y1 and R2Y14 receptors in mice // Pulm. Pharmacol. Ther. – 2017; 45: 62–8. DOI: 10.1016/j.pupt.2017.05.005.
  35. Amison R., Jamshidi S., Rahman K. et al. Diverse signaling of the platelet R2Y1 receptor leads to a dichotomy in platelet function // Eur. J. Pharmacol. – 2018; 827: 58–70. DOI: 10.1016/j.ejphar.2018.03.014.
  36. Liverani E., Rico M., Tsygankov A. et al. R2Y12 receptor modulates sepsis-induced inflammation // Arterioscler. Thromb. Vasc. Biol. – 2016; 36 (5): 961–71. DOI: 10.1161/ATVBAHA.116.307401.
  37. Harden T., Sesma J., Fricks I. et al. Signalling and pharmacological properties of the R2Y receptor // Acta Physiol. (Oxf). – 2010; 199 (2): 149–60. DOI: 10.1111/j.1748-1716.2010.02116.x.
  38. Scrivens M., Dickenson J. Functional expression of the R2Y14 receptor in human neutrophils // Eur. J. Pharmacol. – 2006; 543 (1–3): 166–73. DOI: 10.1016/j.ejphar.2006.05.037.
  39. Sivaramakrishnan V., Bidula S., Campwala H. et al. Constitutive lysosome exocytosis releases ATP and engages R2Y receptors in human monocytes // J. Cell Sci. – 2012; 125 (Pt 19): 4567–75. DOI: 10.1242/jcs.107318.
  40. Kawamura H., Kawamura T., Kanda Y. et al. Extracellular ATP-stimulated macrophages produce macrophage inflammatory protein-2 which is important for neutrophil migration // Immunology. – 2012; 136 (4): 448–58. DOI: 10.1016/S1470-2045(18)30837-4.
  41. Amati A., Zakrzewicz A., Siebers R. et al. Chemokines (CCL3, CCL4, and CCL5) inhibit ATP-induced release of IL-1β by monocytic cells // Mediators Inflamm. – 2017; 2017: 1434872. DOI: 10.1155/2017/1434872.
  42. Satonaka H., Nagata D., Takahashi M. et al. Involvement of R2Y12 receptor in vascular smooth muscle inflammatory changes via MCP-1 upregulation and monocyte adhesion // Am. J. Physiol. Heart Circ. Physiol. – 2015; 308 (8): H853–61. DOI: 10.1152/ajpheart.00862.2013.
  43. Lohman A., Leskov I., Butcher J. et al. Pannexin 1 channels regulate leukocyte emigration through the venous endothelium during acute inflammation // Nat. Commun. – 2015; 6: 7965. DOI: 10.1038/ncomms8965.
  44. Cardoso T., Pompeu T. Silva C. The R2Y1 receptor-mediated leukocyte adhesion to endothelial cells is inhibited by melatonin // Purinergic. Signal. – 2017; 13 (3): 331–8. DOI: 10.1007/s11302-017-9565-4.
  45. Liverani E., Rico M., Garcia A. et al. Prasugrel metabolites inhibit neutrophil functions // J. Pharmacol. Exp. Ther. – 2013; 344 (1): 231–43. DOI: 10.1124/jpet.112.195883.