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Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses

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Abstract

Extracellular ATP and related nucleotides promote a wide range of pathophysiological responses via activation of cell surface purinergic P2 receptors. Almost every cell type expresses P2 receptors and/or exhibit regulated release of ATP. In this review, we focus on the purinergic receptor distribution in inflammatory cells and their implication in diverse immune responses by providing an overview of the current knowledge in the literature related to purinergic signaling in neutrophils, macrophages, dendritic cells, lymphocytes, eosinophils, and mast cells. The pathophysiological role of purinergic signaling in these cells include among others calcium mobilization, actin polymerization, chemotaxis, release of mediators, cell maturation, cytotoxicity, and cell death. We finally discuss the therapeutic potential of P2 receptor subtype selective drugs in inflammatory conditions.

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Abbreviations

cAMP:

Cyclic adenosine monophosphate

DCs:

Dendritic cells

ECP:

Eosinophil cationic protein

ERK:

Extracellular signal-regulated kinases

fMLP:

fMet-Leu-Phe receptor

HLMC:

Human lung mast cell

HMC:

Human mast cell

IP3 :

Inositol 1,4,5-triphosphate

LAD 2:

Leukocyte adhesion deficiency

LCL:

Lymphoblastoid cell lines

MIP-2:

Macrophage inflammatory protein-2

MoDCs:

Monocyte-derived dendritic cells

MSU:

Monosodium urate

E-NTPDase1:

Ecto-nucleoside triphosphate diphosphohydrolase 1

PLC:

Phospholipase C

References

  1. Lotze MT, Zeh HJ, Rubartelli A, Sparvero LJ, Amoscato AA et al (2007) The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity. Immunol Rev 220:60–81

    Article  PubMed  CAS  Google Scholar 

  2. Rubartelli A, Lotze MT (2007) Inside, outside, upside down: damage-associated molecular-pattern molecules (DAMPs) and redox. Trends Immunol 28(10):429–436

    Article  PubMed  CAS  Google Scholar 

  3. Khakh BS, North RA (2006) P2X receptors as cell-surface ATP sensors in health and disease. Nature 442(7102):527–532

    Article  PubMed  CAS  Google Scholar 

  4. Myrtek D, Idzko M (2007) Chemotactic activity of extracellular nucleotideson human immune cells. Purinergic Signal 3(1–2):5–11

    Article  PubMed  CAS  Google Scholar 

  5. Vitiello L, Gorini S, Rosano G, la Sala A (2012) Immunoregulation through extracellular nucleotides. Blood 120(3):511–518

    Google Scholar 

  6. Weber FC, Esser PR, Muller T, Ganesan J, Pellegatti P et al (2010) Lack of the purinergic receptor P2X(7) results in resistance to contact hypersensitivity. J Exp Med 207(12):2609–2619

    Article  PubMed  CAS  Google Scholar 

  7. Wilhelm K, Ganesan J, Muller T, Durr C, Grimm M et al (2010) Graft-versus-host disease is enhanced by extracellular ATP activating P2X7R. Nat Med 16(12):1434–1438

    Article  PubMed  CAS  Google Scholar 

  8. Barbera-Cremades M, Baroja-Mazo A, Gomez AI, Machado F, Di Virgilio F et al (2012) P2X7 receptor-stimulation causes fever via PGE2 and IL-1beta release. FASEB J 26(7):2951–2962

    Article  PubMed  CAS  Google Scholar 

  9. Di Virgilio F, Chiozzi P, Ferrari D, Falzoni S, Sanz JM et al (2001) Nucleotide receptors: an emerging family of regulatory molecules in blood cells. Blood 97(3):587–600

    Article  PubMed  CAS  Google Scholar 

  10. Ferrari D, la Sala A, Panther E, Norgauer J, Di Virgilio F et al (2006) Activation of human eosinophils via P2 receptors: novel findings and future perspectives. J Leukoc Biol 79(1):7–15

    Google Scholar 

  11. Bodin P, Burnstock G (2001) Purinergic signalling: ATP release. Neurochem Res 26(8–9):959–969

    Article  PubMed  CAS  Google Scholar 

  12. Junger WG (2011) Immune cell regulation by autocrine purinergic signalling. Nat Rev Immunol 11(3):201–212

    Article  PubMed  CAS  Google Scholar 

  13. Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL et al (2006) International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol Rev 58(3):281–341

    Article  PubMed  CAS  Google Scholar 

  14. Jarvis MF, Khakh BS (2009) ATP-gated P2X cation-channels. Neuropharmacology 56(1):208–215

    Article  PubMed  CAS  Google Scholar 

  15. Burnstock G , Knight GE (2004) Cellular distribution and functions of P2 receptor subtypes in different systems. Int Rev Cytol 240:31–304

    Google Scholar 

  16. Burnstock G (2007) Purine and pyrimidine receptors. Cell Mol Life Sci 64(12):1471–1483

    Article  PubMed  CAS  Google Scholar 

  17. Volonte C, Amadio S, D'Ambrosi N, Colpi M, Burnstock G (2006) P2 receptor web: complexity and fine-tuning. Pharmacol Ther 112(1):264–280

    Article  PubMed  CAS  Google Scholar 

  18. Rayah A, Kanellopoulos JM, Di Virgilio F (2012) P2 receptors and immunity. Microbes Infect 14(14):1254–1262

    Article  PubMed  CAS  Google Scholar 

  19. Mohanty JG, Raible DG, McDermott LJ, Pelleg A, Schulman ES (2001) Effects of purine and pyrimidine nucleotides on intracellular Ca2+ in human eosinophils: activation of purinergic P2Y receptors. J Allergy Clin Immunol 107(5):849–855

    Article  PubMed  CAS  Google Scholar 

  20. Sak K, Boeynaems JM, Everaus H (2003) Involvement of P2Y receptors in the differentiation of haematopoietic cells. J Leukoc Biol 73(4):442–447

    Article  PubMed  CAS  Google Scholar 

  21. Jin J, Dasari VR, Sistare FD, Kunapuli SP (1998) Distribution of P2Y receptor subtypes on haematopoietic cells. Br J Pharmacol 123(5):789–794

    Article  PubMed  CAS  Google Scholar 

  22. Bulanova E, Budagian V, Orinska Z, Hein M, Petersen F et al (2005) Extracellular ATP induces cytokine expression and apoptosis through P2X7 receptor in murine mast cells. J Immunol 174(7):3880–3890

    PubMed  CAS  Google Scholar 

  23. Feng C, Mery AG, Beller EM, Favot C, Boyce JA (2004) Adenine nucleotides inhibit cytokine generation by human mast cells through a Gs-coupled receptor. J Immunol 173(12):7539–7547

    PubMed  CAS  Google Scholar 

  24. Humphreys BD, Dubyak GR (1998) Modulation of P2X7 nucleotide receptor expression by pro- and anti-inflammatory stimuli in THP-1 monocytes. J Leukoc Biol 64(2):265–273

    PubMed  CAS  Google Scholar 

  25. Gu B, Bendall LJ, Wiley JS (1998) Adenosine triphosphate-induced shedding of CD23 and l-selectin (CD62L) from lymphocytes is mediated by the same receptor but different metalloproteases. Blood 92(3):946–951

    PubMed  CAS  Google Scholar 

  26. Chen JR, Gu BJ, Dao LP, Bradley CJ, Mulligan SP et al (1999) Transendothelial migration of lymphocytes in chronic lymphocytic leukaemia is impaired and involved down-regulation of both l-selectin and CD23. Br J Haematol 105(1):181–189

    Article  PubMed  CAS  Google Scholar 

  27. Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A (2012) Neutrophil function: from mechanisms to disease. Annu Rev Immunol 30:459–489

    Google Scholar 

  28. Sadik CD, Kim ND, Luster AD (2011) Neutrophils cascading their way to inflammation. Trends Immunol 32(10):452–460

    Article  PubMed  CAS  Google Scholar 

  29. Axtell RA, Sandborg RR, Smolen JE, Ward PA, Boxer LA (1990) Exposure of human neutrophils to exogenous nucleotides causes elevation in intracellular calcium, transmembrane calcium fluxes, and an alteration of a cytosolic factor resulting in enhanced superoxide production in response to FMLP and arachidonic acid. Blood 75(6):1324–1332

    PubMed  CAS  Google Scholar 

  30. Ward PA, Cunningham TW, McCulloch KK, Johnson KJ (1988) Regulatory effects of adenosine and adenine nucleotides on oxygen radical responses of neutrophils. Lab Investig 58(4):438–447

    PubMed  CAS  Google Scholar 

  31. Ward PA, Cunningham TW, McCulloch KK, Phan SH, Powell J et al (1988) Platelet enhancement of O2−. responses in stimulated human neutrophils. Identification of platelet factor as adenine nucleotide. Lab Investig 58(1):37–47

    PubMed  CAS  Google Scholar 

  32. Bengtsson T, Zalavary S, Stendahl O, Grenegard M (1996) Release of oxygen metabolites from chemoattractant-stimulated neutrophils is inhibited by resting platelets: role of extracellular adenosine and actin polymerization. Blood 87(10):4411–4423

    PubMed  CAS  Google Scholar 

  33. Zalavary S, Grenegard M, Stendahl O, Bengtsson T (1996) Platelets enhance Fc(gamma) receptor-mediated phagocytosis and respiratory burst in neutrophils: the role of purinergic modulation and actin polymerization. J Leukoc Biol 60(1):58–68

    PubMed  CAS  Google Scholar 

  34. Suh BC, Kim JS, Namgung U, Ha H, Kim KT (2001) P2X7 nucleotide receptor mediation of membrane pore formation and superoxide generation in human promyelocytes and neutrophils. J Immunol 166(11):6754–6763

    PubMed  CAS  Google Scholar 

  35. Vaughan KR, Stokes L, Prince LR, Marriott HM, Meis S et al (2007) Inhibition of neutrophil apoptosis by ATP is mediated by the P2Y11 receptor. J Immunol 179(12):8544–8553

    PubMed  CAS  Google Scholar 

  36. Martel-Gallegos G, Rosales-Saavedra MT, Reyes JP, Casas-Pruneda G, Toro-Castillo C et al (2010) Human neutrophils do not express purinergic P2X7 receptors. Purinergic Signal 6(3):297–306

    Article  PubMed  CAS  Google Scholar 

  37. Abbracchio MP, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C et al (2003) Characterization of the UDP-glucose receptor (re-named here the P2Y14 receptor) adds diversity to the P2Y receptor family. Trends Pharmacol Sci 24(2):52–55

    Article  PubMed  CAS  Google Scholar 

  38. Chen Y, Shukla A, Namiki S, Insel PA, Junger WG (2004) A putative osmoreceptor system that controls neutrophil function through the release of ATP, its conversion to adenosine, and activation of A2 adenosine and P2 receptors. J Leukoc Biol 76(1):245–253

    Article  PubMed  CAS  Google Scholar 

  39. Moore DJ, Murdock PR, Watson JM, Faull RL, Waldvogel HJ et al (2003) GPR105, a novel Gi/o-coupled UDP-glucose receptor expressed on brain glia and peripheral immune cells, is regulated by immunologic challenge: possible role in neuroimmune function. Brain Res Mol Brain Res 118(1–2):10–23

    Article  PubMed  CAS  Google Scholar 

  40. Meshki J, Tuluc F, Bredetean O, Ding Z, Kunapuli SP (2004) Molecular mechanism of nucleotide-induced primary granule release in human neutrophils: role for the P2Y2 receptor. Am J Physiol Cell Physiol 286(2):C264–C271

    Article  PubMed  CAS  Google Scholar 

  41. Scrivens M, Dickenson JM (2006) Functional expression of the P2Y14 receptor in human neutrophils. Eur J Pharmacol 543(1–3):166–173

    Article  PubMed  CAS  Google Scholar 

  42. Ben YF, Kukulski F, Tremblay A, Sevigny J (2009) Concomitant activation of P2Y(2) and P2Y(6) receptors on monocytes is required for TLR1/2-induced neutrophil migration by regulating IL-8 secretion. Eur J Immunol 39(10):2885–2894

    Article  CAS  Google Scholar 

  43. Lecut C, Frederix K, Johnson DM, Deroanne C, Thiry M et al (2009) P2X1 ion channels promote neutrophil chemotaxis through rho kinase activation. J Immunol 183(4):2801–2809

    Article  PubMed  CAS  Google Scholar 

  44. Ward PA, Cunningham TW, Johnson KJ (1989) Signal transduction events in stimulated rat neutrophils: effects of adenine nucleotides. Clin Immunol Immunopathol 50(1 Pt 1):30–41

    Article  PubMed  CAS  Google Scholar 

  45. Cowen DS, Lazarus HM, Shurin SB, Stoll SE, Dubyak GR (1989) Extracellular adenosine triphosphate activates calcium mobilization in human phagocytic leukocytes and neutrophil/monocyte progenitor cells. J Clin Invest 83(5):1651–1660

    Article  PubMed  CAS  Google Scholar 

  46. Dubyak GR, Cowen DS, Lazarus HM (1988) Activation of the inositol phospholipid signaling system by receptors for extracellular ATP in human neutrophils, monocytes, and neutrophil/monocyte progenitor cells. Ann N Y Acad Sci 551:218–237

    Google Scholar 

  47. Kuhns DB, Wright DG, Nath J, Kaplan SS, Basford RE (1988) ATP induces transient elevations of [Ca2+]i in human neutrophils and primes these cells for enhanced O2− generation. Lab Investig 58(4):448–453

    PubMed  CAS  Google Scholar 

  48. Merritt JE, Moores KE (1991) Human neutrophils have a novel purinergic P2-type receptor linked to calcium mobilization. Cell Signal 3(3):243–249

    Article  PubMed  CAS  Google Scholar 

  49. Krause KH, Campbell KP, Welsh MJ, Lew DP (1990) The calcium signal and neutrophil activation. Clin Biochem 23(2):159–166

    Article  PubMed  CAS  Google Scholar 

  50. Meshki J, Tuluc F, Bredetean O, Garcia A, Kunapuli SP (2006) Signaling pathways downstream of P2 receptors in human neutrophils. Purinergic Signal 2(3):537–544

    Article  PubMed  CAS  Google Scholar 

  51. Chen Y, Yao Y, Sumi Y, Li A, To UK et al (2010) Purinergic signaling: a fundamental mechanism in neutrophil activation. Sci Signal 3(125):ra45

    Article  PubMed  CAS  Google Scholar 

  52. Verghese MW, Kneisler TB, Boucheron JA (1996) P2U agonists induce chemotaxis and actin polymerization in human neutrophils and differentiated HL60 cells. J Biol Chem 271(26):15597–15601

    Article  PubMed  CAS  Google Scholar 

  53. Becker EL, Kermode JC, Naccache PH, Yassin R, Marsh ML et al (1985) The inhibition of neutrophil granule enzyme secretion and chemotaxis by pertussis toxin. J Cell Biol 100(5):1641–1646

    Article  PubMed  CAS  Google Scholar 

  54. Junger WG (2008) Purinergic regulation of neutrophil chemotaxis. Cell Mol Life Sci 65(16):2528–2540

    Article  PubMed  CAS  Google Scholar 

  55. Chen Y, Corriden R, Inoue Y, Yip L, Hashiguchi N et al (2006) ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors. Science 314(5806):1792–1795

    Article  PubMed  CAS  Google Scholar 

  56. Inoue Y, Chen Y, Hirsh MI, Yip L, Junger WG (2008) A3 and P2Y2 receptors control the recruitment of neutrophils to the lungs in a mouse model of sepsis. Shock 30(2):173–177

    PubMed  Google Scholar 

  57. Kukulski F, Ben YF, Lecka J, Kauffenstein G, Levesque SA et al (2009) Extracellular ATP and P2 receptors are required for IL-8 to induce neutrophil migration. Cytokine 46(2):166–170

    Article  PubMed  CAS  Google Scholar 

  58. Kukulski F, Bahrami F, Ben YF, Lecka J, Martin-Satue M et al (2011) NTPDase1 controls IL-8 production by human neutrophils. J Immunol 187(2):644–653

    Article  PubMed  CAS  Google Scholar 

  59. Corriden R, Chen Y, Inoue Y, Beldi G, Robson SC et al (2008) Ecto-nucleoside triphosphate diphosphohydrolase 1 (E-NTPDase1/CD39) regulates neutrophil chemotaxis by hydrolyzing released ATP to adenosine. J Biol Chem 283(42):28480–28486

    Article  PubMed  CAS  Google Scholar 

  60. Kukulski F, Ben YF, Lefebvre J, Warny M, Tessier PA et al (2007) Extracellular nucleotides mediate LPS-induced neutrophil migration in vitro and in vivo. J Leukoc Biol 81(5):1269–1275

    Article  PubMed  Google Scholar 

  61. Kukulski F, Ben YF, Bahrami F, Fausther M, Tremblay A et al (2010) Endothelial P2Y2 receptor regulates LPS-induced neutrophil transendothelial migration in vitro. Mol Immunol 47(5):991–999

    Article  PubMed  CAS  Google Scholar 

  62. Kawamura H, Kawamura T, Kanda Y, Kobayashi T, Abo T (2012) Extracellular ATP-stimulated macrophages produce macrophage inflammatory protein-2 which is important for neutrophil migration. Immunology 136(4):448–458

    Article  PubMed  CAS  Google Scholar 

  63. Lu DJ, Grinstein S (1990) ATP and guanine nucleotide dependence of neutrophil activation. Evidence for the involvement of two distinct GTP-binding proteins. J Biol Chem 265(23):13721–13729

    PubMed  CAS  Google Scholar 

  64. Eltzschig HK, Eckle T, Mager A, Kuper N, Karcher C et al (2006) ATP release from activated neutrophils occurs via connexin 43 and modulates adenosine-dependent endothelial cell function. Circ Res 99(10):1100–1108

    Article  PubMed  CAS  Google Scholar 

  65. Underhill DM, Goodridge HS (2012) Information processing during phagocytosis. Nat Rev Immunol 12(7):492–502

    Article  PubMed  CAS  Google Scholar 

  66. Murray PJ, Wynn TA (2011) Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 11(11):723–737

    Article  PubMed  CAS  Google Scholar 

  67. Cohn ZA, Parks E (1967) The regulation of pinocytosis in mouse macrophages. 3. The induction of vesicle formation by nucleosides and nucleotides. J Exp Med 125(3):457–466

    Article  PubMed  CAS  Google Scholar 

  68. Buisman HP, Steinberg TH, Fischbarg J, Silverstein SC, Vogelzang SA et al (1988) Extracellular ATP induces a large nonselective conductance in macrophage plasma membranes. Proc Natl Acad Sci U S A 85(21):7988–7992

    Article  PubMed  CAS  Google Scholar 

  69. Greenberg S, Di Virgilio F, Steinberg TH, Silverstein SC (1988) Extracellular nucleotides mediate Ca2+ fluxes in J774 macrophages by two distinct mechanisms. J Biol Chem 263(21):10337–10343

    PubMed  CAS  Google Scholar 

  70. Steinberg TH, Silverstein SC (1987) Extracellular ATP4− promotes cation fluxes in the J774 mouse macrophage cell line. J Biol Chem 262(7):3118–3122

    PubMed  CAS  Google Scholar 

  71. Sung SS, Young JD, Origlio AM, Heiple JM, Kaback HR et al (1985) Extracellular ATP perturbs transmembrane ion fluxes, elevates cytosolic [Ca2+], and inhibits phagocytosis in mouse macrophages. J Biol Chem 260(25):13442–13449

    PubMed  CAS  Google Scholar 

  72. Surprenant A, Rassendren F, Kawashima E, North RA, Buell G (1996) The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272(5262):735–738

    Article  PubMed  CAS  Google Scholar 

  73. Falzoni S, Munerati M, Ferrari D, Spisani S, Moretti S et al (1995) The purinergic P2Z receptor of human macrophage cells. Characterization and possible physiological role. J Clin Invest 95(3):1207–1216

    Article  PubMed  CAS  Google Scholar 

  74. Hickman SE, el KJ, Greenberg S, Schieren I, Silverstein SC (1994) P2Z adenosine triphosphate receptor activity in cultured human monocyte-derived macrophages. Blood 84(8):2452–2456

    PubMed  CAS  Google Scholar 

  75. Bowler JW, Bailey RJ, North RA, Surprenant A (2003) P2X4, P2Y1 and P2Y2 receptors on rat alveolar macrophages. Br J Pharmacol 140(3):567–575

    Article  PubMed  CAS  Google Scholar 

  76. Coutinho-Silva R, Ojcius DM, Gorecki DC, Persechini PM, Bisaggio RC et al (2005) Multiple P2X and P2Y receptor subtypes in mouse J774, spleen and peritoneal macrophages. Biochem Pharmacol 69(4):641–655

    Article  PubMed  CAS  Google Scholar 

  77. Bar I, Guns PJ, Metallo J, Cammarata D, Wilkin F et al (2008) Knockout mice reveal a role for P2Y6 receptor in macrophages, endothelial cells, and vascular smooth muscle cells. Mol Pharmacol 74(3):777–784

    Article  PubMed  CAS  Google Scholar 

  78. Myrtek D, Muller T, Geyer V, Derr N, Ferrari D et al (2008) Activation of human alveolar macrophages via P2 receptors: coupling to intracellular Ca2+ increases and cytokine secretion. J Immunol 181(3):2181–2188

    PubMed  CAS  Google Scholar 

  79. Fujiwara N, Kobayashi K (2005) Macrophages in inflammation. Curr Drug Targets Inflamm Allergy 4(3):281–286

    Article  PubMed  CAS  Google Scholar 

  80. Tonetti M, Sturla L, Bistolfi T, Benatti U, De Flora A (1994) Extracellular ATP potentiates nitric oxide synthase expression induced by lipopolysaccharide in RAW 264.7 murine macrophages. Biochem Biophys Res Commun 203(1):430–435

    Article  PubMed  CAS  Google Scholar 

  81. Tonetti M, Sturla L, Giovine M, Benatti U, De Flora A (1995) Extracellular ATP enhances mRNA levels of nitric oxide synthase and TNF-alpha in lipopolysaccharide-treated RAW 264.7 murine macrophages. Biochem Biophys Res Commun 214(1):125–130

    Article  PubMed  CAS  Google Scholar 

  82. Perregaux D, Gabel CA (1994) Interleukin-1 beta maturation and release in response to ATP and nigericin. Evidence that potassium depletion mediated by these agents is a necessary and common feature of their activity. J Biol Chem 269(21):15195–15203

    PubMed  CAS  Google Scholar 

  83. Lemaire I, Leduc N (2003) Purinergic P2X7 receptor function in lung alveolar macrophages: pharmacologic characterization and bidirectional regulation by Th1 and Th2 cytokines. Drug Dev Res 59(1):118–127

    Article  CAS  Google Scholar 

  84. el-Moatassim C, Dubyak GR (1993) Dissociation of the pore-forming and phospholipase D activities stimulated via P2z purinergic receptors in BAC1.2F5 macrophages. Product inhibition of phospholipase D enzyme activity. J Biol Chem 268(21):15571–15578

    PubMed  CAS  Google Scholar 

  85. Gudipaty L, Munetz J, Verhoef PA, Dubyak GR (2003) Essential role for Ca2+ in regulation of IL-1beta secretion by P2X7 nucleotide receptor in monocytes, macrophages, and HEK-293 cells. Am J Physiol Cell Physiol 285(2):C286–C299

    Article  PubMed  CAS  Google Scholar 

  86. Perregaux DG, Laliberte RE, Gabel CA (1996) Human monocyte interleukin-1beta posttranslational processing. Evidence of a volume-regulated response. J Biol Chem 271(47):29830–29838

    Article  PubMed  CAS  Google Scholar 

  87. Ferrari D, Chiozzi P, Falzoni S, Dal Susino M, Melchiorri L et al (1997) Extracellular ATP triggers IL-1 beta release by activating the purinergic P2Z receptor of human macrophages. J Immunol 159(3):1451–1458

    PubMed  CAS  Google Scholar 

  88. Pelegrin P, Barroso-Gutierrez C, Surprenant A (2008) P2X7 receptor differentially couples to distinct release pathways for IL-1beta in mouse macrophage. J Immunol 180(11):7147–7157

    PubMed  CAS  Google Scholar 

  89. Verhoef PA, Kertesy SB, Lundberg K, Kahlenberg JM, Dubyak GR (2005) Inhibitory effects of chloride on the activation of caspase-1, IL-1beta secretion, and cytolysis by the P2X7 receptor. J Immunol 175(11):7623–7634

    PubMed  CAS  Google Scholar 

  90. Mariathasan S, Weiss DS, Newton K, McBride J, O'Rourke K et al (2006) Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440(7081):228–232

    Article  PubMed  CAS  Google Scholar 

  91. Di Virgilio F (2007) Liaisons dangereuses: P2X(7) and the inflammasome. Trends Pharmacol Sci 28(9):465–472

    Article  PubMed  CAS  Google Scholar 

  92. Babelova A, Moreth K, Tsalastra-Greul W, Zeng-Brouwers J, Eickelberg O et al (2009) Biglycan, a danger signal that activates the NLRP3 inflammasome via toll-like and P2X receptors. J Biol Chem 284(36):24035–24048

    Article  PubMed  CAS  Google Scholar 

  93. Niemi K, Teirila L, Lappalainen J, Rajamaki K, Baumann MH et al (2011) Serum amyloid A activates the NLRP3 inflammasome via P2X7 receptor and a cathepsin B-sensitive pathway. J Immunol 186(11):6119–6128

    Article  PubMed  CAS  Google Scholar 

  94. Petrilli V, Papin S, Dostert C, Mayor A, Martinon F et al (2007) Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ 14(9):1583–1589

    Article  PubMed  CAS  Google Scholar 

  95. Franchi L, Kanneganti TD, Dubyak GR, Nunez G (2007) Differential requirement of P2X7 receptor and intracellular K+ for caspase-1 activation induced by intracellular and extracellular bacteria. J Biol Chem 282(26):18810–18818

    Article  PubMed  CAS  Google Scholar 

  96. Cruz CM, Rinna A, Forman HJ, Ventura AL, Persechini PM et al (2007) ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages. J Biol Chem 282(5):2871–2879

    Article  PubMed  CAS  Google Scholar 

  97. Sekiyama A, Ueda H, Kashiwamura S, Sekiyama R, Takeda M et al (2005) A stress-induced, superoxide-mediated caspase-1 activation pathway causes plasma IL-18 upregulation. Immunity 22(6):669–677

    Article  PubMed  CAS  Google Scholar 

  98. Chiozzi P, Murgia M, Falzoni S, Ferrari D, Di Virgilio F (1996) Role of the purinergic P2Z receptor in spontaneous cell death in J774 macrophage cultures. Biochem Biophys Res Commun 218(1):176–181

    Article  PubMed  CAS  Google Scholar 

  99. Le Feuvre RA, Brough D, Iwakura Y, Takeda K, Rothwell NJ (2002) Priming of macrophages with lipopolysaccharide potentiates P2X7-mediated cell death via a caspase-1-dependent mechanism, independently of cytokine production. J Biol Chem 277(5):3210–3218

    Article  PubMed  CAS  Google Scholar 

  100. Biswas D, Qureshi OS, Lee WY, Croudace JE, Mura M et al. (2008) ATP-induced autophagy is associated with rapid killing of intracellular mycobacteria within human monocytes/macrophages. BMC Immunol 9:35

    Google Scholar 

  101. Ernst RK, Guina T, Miller SI (1999) How intracellular bacteria survive: surface modifications that promote resistance to host innate immune responses. J Infect Dis 179(Suppl 2):S326–S330

    Article  PubMed  CAS  Google Scholar 

  102. Lammas DA, Stober C, Harvey CJ, Kendrick N, Panchalingam S et al (1997) ATP-induced killing of mycobacteria by human macrophages is mediated by purinergic P2Z(P2X7) receptors. Immunity 7(3):433–444

    Article  PubMed  CAS  Google Scholar 

  103. Punj V, Zaborina O, Dhiman N, Falzari K, Bagdasarian M et al (2000) Phagocytic cell killing mediated by secreted cytotoxic factors of Vibrio cholerae. Infect Immun 68(9):4930–4937

    Article  PubMed  CAS  Google Scholar 

  104. Zaborina O, Misra N, Kostal J, Kamath S, Kapatral V et al (1999) P2Z-independent and P2Z receptor-mediated macrophage killing by Pseudomonas aeruginosa isolated from cystic fibrosis patients. Infect Immun 67(10):5231–5242

    PubMed  CAS  Google Scholar 

  105. Coutinho-Silva R, Stahl L, Raymond MN, Jungas T, Verbeke P et al (2003) Inhibition of chlamydial infectious activity due to P2X7R-dependent phospholipase D activation. Immunity 19(3):403–412

    Article  PubMed  CAS  Google Scholar 

  106. Coutinho-Silva R, da Monteiro CC, Persechini PM, Ojcius DM (2007) The role of P2 receptors in controlling infections by intracellular pathogens. Purinergic Signal 3(1–2):83–90

    Article  PubMed  CAS  Google Scholar 

  107. Coutinho-Silva R, Correa G, Sater AA, Ojcius DM (2009) The P2X(7) receptor and intracellular pathogens: a continuing struggle. Purinergic Signal 5(2):197–204

    Article  PubMed  CAS  Google Scholar 

  108. Kawano A, Tsukimoto M, Mori D, Noguchi T, Harada H et al (2012) Regulation of P2X7-dependent inflammatory functions by P2X4 receptor in mouse macrophages. Biochem Biophys Res Commun 420(1):102–107

    Article  PubMed  CAS  Google Scholar 

  109. Kawano A, Tsukimoto M, Noguchi T, Hotta N, Harada H et al (2012) Involvement of P2X4 receptor in P2X7 receptor-dependent cell death of mouse macrophages. Biochem Biophys Res Commun 419(2):374–380

    Article  PubMed  CAS  Google Scholar 

  110. Levesque SA, Kukulski F, Enjyoji K, Robson SC, Sevigny J (2010) NTPDase1 governs P2X7-dependent functions in murine macrophages. Eur J Immunol 40(5):1473–1485

    Article  PubMed  CAS  Google Scholar 

  111. Qu Y, Franchi L, Nunez G, Dubyak GR (2007) Nonclassical IL-1 beta secretion stimulated by P2X7 receptors is dependent on inflammasome activation and correlated with exosome release in murine macrophages. J Immunol 179(3):1913–1925

    PubMed  CAS  Google Scholar 

  112. Lopez-Castejon G, Theaker J, Pelegrin P, Clifton AD, Braddock M et al (2010) P2X(7) receptor-mediated release of cathepsins from macrophages is a cytokine-independent mechanism potentially involved in joint diseases. J Immunol 185(4):2611–2619

    Article  PubMed  CAS  Google Scholar 

  113. Moore SF, MacKenzie AB (2007) Murine macrophage P2X7 receptors support rapid prothrombotic responses. Cell Signal 19(4):855–866

    Article  PubMed  CAS  Google Scholar 

  114. Gu BJ, Wiley JS (2006) Rapid ATP-induced release of matrix metalloproteinase 9 is mediated by the P2X7 receptor. Blood 107(12):4946–4953

    Article  PubMed  CAS  Google Scholar 

  115. Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A et al (2009) Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461(7261):282–286

    Article  PubMed  CAS  Google Scholar 

  116. McCloskey MA, Fan Y, Luther S (1999) Chemotaxis of rat mast cells toward adenine nucleotides. J Immunol 163(2):970–977

    PubMed  CAS  Google Scholar 

  117. Kronlage M, Song J, Sorokin L, Isfort K, Schwerdtle T et al (2010) Autocrine purinergic receptor signaling is essential for macrophage chemotaxis. Sci Signal 3(132):ra55

    Article  PubMed  CAS  Google Scholar 

  118. Isfort K, Ebert F, Bornhorst J, Sargin S, Kardakaris R et al (2011) Real-time imaging reveals that P2Y2 and P2Y12 receptor agonists are not chemoattractants and macrophage chemotaxis to complement C5a is phosphatidylinositol 3-kinase (PI3K)- and p38 mitogen-activated protein kinase (MAPK)-independent. J Biol Chem 286(52):44776–44787

    Article  PubMed  CAS  Google Scholar 

  119. Marques-da-Silva C, Burnstock G, Ojcius DM, Coutinho-Silva R (2011) Purinergic receptor agonists modulate phagocytosis and clearance of apoptotic cells in macrophages. Immunobiology 216(1–2):1–11

    Article  PubMed  CAS  Google Scholar 

  120. Chiozzi P, Sanz JM, Ferrari D, Falzoni S, Aleotti A et al (1997) Spontaneous cell fusion in macrophage cultures expressing high levels of the P2Z/P2X7 receptor. J Cell Biol 138(3):697–706

    Article  PubMed  CAS  Google Scholar 

  121. Lemaire I, Falzoni S, Leduc N, Zhang B, Pellegatti P et al (2006) Involvement of the purinergic P2X7 receptor in the formation of multinucleated giant cells. J Immunol 177(10):7257–7265

    PubMed  CAS  Google Scholar 

  122. Summers dL, Gommerman JL (2012) Fine-tuning of dendritic cell biology by the TNF superfamily. Nat Rev Immunol 12(5):339–351

    Google Scholar 

  123. Berchtold S, Ogilvie AL, Bogdan C, Muhl-Zurbes P, Ogilvie A et al (1999) Human monocyte derived dendritic cells express functional P2X and P2Y receptors as well as ecto-nucleotidases. FEBS Lett 458(3):424–428

    Article  PubMed  CAS  Google Scholar 

  124. Ferrari D, la Sala A, Chiozzi P, Morelli A, Falzoni S et al (2000) The P2 purinergic receptors of human dendritic cells: identification and coupling to cytokine release. FASEB J 14(15):2466–2476

    Article  PubMed  CAS  Google Scholar 

  125. Schnurr M, Toy T, Stoitzner P, Cameron P, Shin A et al (2003) ATP gradients inhibit the migratory capacity of specific human dendritic cell types: implications for P2Y11 receptor signaling. Blood 102(2):613–620

    Article  PubMed  CAS  Google Scholar 

  126. Skelton L, Cooper M, Murphy M, Platt A (2003) Human immature monocyte-derived dendritic cells express the G protein-coupled receptor GPR105 (KIAA0001, P2Y14) and increase intracellular calcium in response to its agonist, uridine diphosphoglucose. J Immunol 171(4):1941–1949

    PubMed  CAS  Google Scholar 

  127. Buell G, Chessell IP, Michel AD, Collo G, Salazzo M et al (1998) Blockade of human P2X7 receptor function with a monoclonal antibody. Blood 92(10):3521–3528

    PubMed  CAS  Google Scholar 

  128. Wilkin F, Duhant X, Bruyns C, Suarez-Huerta N, Boeynaems JM et al (2001) The P2Y11 receptor mediates the ATP-induced maturation of human monocyte-derived dendritic cells. J Immunol 166(12):7172–7177

    PubMed  CAS  Google Scholar 

  129. la Sala A, Ferrari D, Corinti S, Cavani A, Di Virgilio F et al (2001) Extracellular ATP induces a distorted maturation of dendritic cells and inhibits their capacity to initiate Th1 responses. J Immunol 166(3):1611–1617

    PubMed  CAS  Google Scholar 

  130. Wilkin F, Stordeur P, Goldman M, Boeynaems JM, Robaye B (2002) Extracellular adenine nucleotides modulate cytokine production by human monocyte-derived dendritic cells: dual effect on IL-12 and stimulation of IL-10. Eur J Immunol 32(9):2409–2417

    Article  PubMed  CAS  Google Scholar 

  131. Marteau F, Communi D, Boeynaems JM, Suarez GN (2004) Involvement of multiple P2Y receptors and signaling pathways in the action of adenine nucleotides diphosphates on human monocyte-derived dendritic cells. J Leukoc Biol 76(4):796–803

    Article  PubMed  CAS  Google Scholar 

  132. Schnurr M, Toy T, Shin A, Wagner M, Cebon J et al (2005) Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway. Blood 105(4):1582–1589

    Article  PubMed  CAS  Google Scholar 

  133. Schnurr M, Then F, Galambos P, Scholz C, Siegmund B et al (2000) Extracellular ATP and TNF-alpha synergize in the activation and maturation of human dendritic cells. J Immunol 165(8):4704–4709

    PubMed  CAS  Google Scholar 

  134. Ben AA, Cammarata D, Conley PB, Boeynaems JM, Robaye B (2010) Role of the P2Y12 receptor in the modulation of murine dendritic cell function by ADP. J Immunol 185(10):5900–5906

    Article  Google Scholar 

  135. Liu QH, Bohlen H, Titzer S, Christensen O, Diehl V et al (1999) Expression and a role of functionally coupled P2Y receptors in human dendritic cells. FEBS Lett 445(2–3):402–408

    Article  PubMed  CAS  Google Scholar 

  136. Coutinho-Silva R, Persechini PM, Bisaggio RD, Perfettini JL, Neto AC et al (1999) P2Z/P2X7 receptor-dependent apoptosis of dendritic cells. Am J Physiol 276(5 Pt 1):C1139–C1147

    PubMed  CAS  Google Scholar 

  137. Nihei OK, de Carvalho AC, Savino W, Alves LA (2000) Pharmacologic properties of P(2Z)/P2X(7)receptor characterized in murine dendritic cells: role on the induction of apoptosis. Blood 96(3):996–1005

    PubMed  CAS  Google Scholar 

  138. Girolomoni G, Santantonio ML, Pastore S, Bergstresser PR, Giannetti A et al (1993) Epidermal Langerhans cells are resistant to the permeabilizing effects of extracellular ATP: in vitro evidence supporting a protective role of membrane ATPase. J Investig Dermatol 100(3):282–287

    Article  PubMed  CAS  Google Scholar 

  139. Idzko M, Dichmann S, Ferrari D, Di Virgilio F, la Sala A et al (2002) Nucleotides induce chemotaxis and actin polymerization in immature but not mature human dendritic cells via activation of pertussis toxin-sensitive P2y receptors. Blood 100(3):925–932

    Article  PubMed  CAS  Google Scholar 

  140. la Sala A, Sebastiani S, Ferrari D, Di Virgilio F, Idzko M et al (2002) Dendritic cells exposed to extracellular adenosine triphosphate acquire the migratory properties of mature cells and show a reduced capacity to attract type 1T lymphocytes. Blood 99(5):1715–1722

    Article  PubMed  CAS  Google Scholar 

  141. Muller T, Robaye B, Vieira RP, Ferrari D, Grimm M et al (2010) The purinergic receptor P2Y2 receptor mediates chemotaxis of dendritic cells and eosinophils in allergic lung inflammation. Allergy 65(12):1545–1553

    Article  PubMed  CAS  Google Scholar 

  142. Idzko M, Hammad H, van NM, Kool M, Willart MA et al (2007) Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells. Nat Med 13(8):913–919

    Article  PubMed  CAS  Google Scholar 

  143. Manthei DM, Jackson DJ, Evans MD, Gangnon RE, Tisler CJ et al (2012) Protection from asthma in a high-risk birth cohort by attenuated P2X(7) function. J Allergy Clin Immunol 130(2):496–502

    Article  PubMed  CAS  Google Scholar 

  144. Islam SA, Luster AD (2012) T cell homing to epithelial barriers in allergic disease. Nat Med 18(5):705–715

    Article  PubMed  CAS  Google Scholar 

  145. Batista FD, Harwood NE (2009) The who, how and where of antigen presentation to B cells. Nat Rev Immunol 9(1):15–27

    Article  PubMed  CAS  Google Scholar 

  146. Vivier E, Ugolini S, Blaise D, Chabannon C, Brossay L (2012) Targeting natural killer cells and natural killer T cells in cancer. Nat Rev Immunol 12(4):239–252

    Article  PubMed  CAS  Google Scholar 

  147. Baricordi OR, Ferrari D, Melchiorri L, Chiozzi P, Hanau S et al (1996) An ATP-activated channel is involved in mitogenic stimulation of human T lymphocytes. Blood 87(2):682–690

    PubMed  CAS  Google Scholar 

  148. Wiley JS, Dubyak GR (1989) Extracellular adenosine triphosphate increases cation permeability of chronic lymphocytic leukemic lymphocytes. Blood 73(5):1316–1323

    PubMed  CAS  Google Scholar 

  149. Padeh S, Cohen A, Roifman CM (1991) ATP-induced activation of human B lymphocytes via P2-purinoceptors. J Immunol 146(5):1626–1632

    PubMed  CAS  Google Scholar 

  150. Conigrave AD, Fernando KC, Gu B, Tasevski V, Zhang W et al (2001) P2Y(11) receptor expression by human lymphocytes: evidence for two cAMP-linked purinoceptors. Eur J Pharmacol 426(3):157–163

    Article  PubMed  CAS  Google Scholar 

  151. Lee DH, Park KS, Kong ID, Kim JW, Han BG (2006) Expression of P2 receptors in human B cells and Epstein-Barr virus-transformed lymphoblastoid cell lines. BMC Immunol 7:22

    Google Scholar 

  152. Sluyter R, Barden JA, Wiley JS (2001) Detection of P2X purinergic receptors on human B lymphocytes. Cell Tissue Res 304(2):231–236

    Article  PubMed  CAS  Google Scholar 

  153. Wang L, Jacobsen SE, Bengtsson A, Erlinge D (2004) P2 receptor mRNA expression profiles in human lymphocytes, monocytes and CD34+ stem and progenitor cells. BMC Immunol 5:16

    Google Scholar 

  154. Scrivens M, Dickenson JM (2005) Functional expression of the P2Y14 receptor in murine T-lymphocytes. Br J Pharmacol 146(3):435–444

    Article  PubMed  CAS  Google Scholar 

  155. Duhant X, Schandene L, Bruyns C, Gonzalez NS, Goldman M et al (2002) Extracellular adenine nucleotides inhibit the activation of human CD4+ T lymphocytes. J Immunol 169(1):15–21

    PubMed  CAS  Google Scholar 

  156. Duhant X, Suarez GN, Schandene L, Goldman M, Communi D et al (2005) Molecular mechanisms of extracellular adenine nucleotides-mediated inhibition of human Cd4(+) T lymphocytes activation. Purinergic Signal 1(4):377–381

    Article  PubMed  CAS  Google Scholar 

  157. el-Moatassim C, Dornand J, Mani JC (1987) Extracellular ATP increases cytosolic free calcium in thymocytes and initiates the blastogenesis of the phorbol 12-myristate 13-acetate-treated medullary population. Biochim Biophys Acta 927(3):437–444

    Article  PubMed  CAS  Google Scholar 

  158. Fishman RF, Rubin AL, Novogrodsky A, Stenzel KH (1980) Selective suppression of blastogenesis induced by different mitogens: effect of noncyclic adenosine-containing compounds. Cell Immunol 54(1):129–139

    Article  PubMed  CAS  Google Scholar 

  159. Gregory S, Kern M (1978) Adenosine and adenine nucleotides are mitogenic for mouse thymocytes. Biochem Biophys Res Commun 83(3):1111–1116

    Article  PubMed  CAS  Google Scholar 

  160. Huang N, Wang DJ, Heppel LA (1989) Extracellular ATP is a mitogen for 3T3, 3T6, and A431 cells and acts synergistically with other growth factors. Proc Natl Acad Sci U S A 86(20):7904–7908

    Article  PubMed  CAS  Google Scholar 

  161. Ikehara S, Pahwa RN, Lunzer DG, Good RA, Modak MJ (1981) Adenosine-5′-triphosphate-(ATP) mediated stimulation and suppression of DNA synthesis in lymphoid cells. I. Characterization of ATP responsive cells in mouse lymphoid organs. J Immunol 127(5):1834–1838

    PubMed  CAS  Google Scholar 

  162. Barankiewicz J, Dosch HM, Cohen A (1988) Extracellular nucleotide catabolism in human B and T lymphocytes. The source of adenosine production. J Biol Chem 263(15):7094–7098

    PubMed  CAS  Google Scholar 

  163. Corriden R, Insel PA, Junger WG (2007) A novel method using fluorescence microscopy for real-time assessment of ATP release from individual cells. Am J Physiol Cell Physiol 293(4):C1420–C1425

    Article  PubMed  CAS  Google Scholar 

  164. Loomis WH, Namiki S, Ostrom RS, Insel PA, Junger WG (2003) Hypertonic stress increases T cell interleukin-2 expression through a mechanism that involves ATP release, P2 receptor, and p38 MAPK activation. J Biol Chem 278(7):4590–4596

    Article  PubMed  CAS  Google Scholar 

  165. Yip L, Cheung CW, Corriden R, Chen Y, Insel PA et al (2007) Hypertonic stress regulates T-cell function by the opposing actions of extracellular adenosine triphosphate and adenosine. Shock 27(3):242–250

    Article  PubMed  CAS  Google Scholar 

  166. Yip L, Woehrle T, Corriden R, Hirsh M, Chen Y et al (2009) Autocrine regulation of T-cell activation by ATP release and P2X7 receptors. FASEB J 23(6):1685–1693

    Article  PubMed  CAS  Google Scholar 

  167. Schenk U, Westendorf AM, Radaelli E, Casati A, Ferro M et al (2008) Purinergic control of T cell activation by ATP released through pannexin-1 hemichannels. Sci Signal 1(39):ra6

    Article  PubMed  CAS  Google Scholar 

  168. Woehrle T, Yip L, Manohar M, Sumi Y, Yao Y et al (2010) Hypertonic stress regulates T cell function via pannexin-1 hemichannels and P2X receptors. J Leukoc Biol 88(6):1181–1189

    Article  PubMed  CAS  Google Scholar 

  169. Schenk U, Frascoli M, Proietti M, Geffers R, Traggiai E et al (2011) ATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors. Sci Signal 4(162):ra12

    Article  PubMed  Google Scholar 

  170. Borsellino G, Kleinewietfeld M, Di Mitri D, Sternjak A, Diamantini A et al (2007) Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 110(4):1225–1232

    Article  PubMed  CAS  Google Scholar 

  171. Wolberg G, Zimmerman TP, Hiemstra K, Winston M, Chu LC (1975) Adenosine inhibition of lymphocyte-mediated cytolysis: possible role of cyclic adenosine monophosphate. Science 187(4180):957–959

    Article  PubMed  CAS  Google Scholar 

  172. Wolberg G, Zimmerman TP, Duncan GS, Singer KH, Elion GB (1978) Inhibition of lymphocyte-mediated cytolysis by adenosine analogs. Biochemical studies concerning mechanism of action. Biochem Pharmacol 27(10):1487–1495

    Article  PubMed  CAS  Google Scholar 

  173. Blanchard DK, Wei S, Duan C, Pericle F, Diaz JI et al (1995) Role of extracellular adenosine triphosphate in the cytotoxic T-lymphocyte-mediated lysis of antigen presenting cells. Blood 85(11):3173–3182

    PubMed  CAS  Google Scholar 

  174. Filippini A, Taffs RE, Sitkovsky MV (1990) Extracellular ATP in T-lymphocyte activation: possible role in effector functions. Proc Natl Acad Sci U S A 87(21):8267–8271

    Article  PubMed  CAS  Google Scholar 

  175. Tsukimoto M, Maehata M, Harada H, Ikari A, Takagi K et al (2006) P2X7 receptor-dependent cell death is modulated during murine T cell maturation and mediated by dual signaling pathways. J Immunol 177(5):2842–2850

    PubMed  CAS  Google Scholar 

  176. Aswad F, Dennert G (2006) P2X7 receptor expression levels determine lethal effects of a purine based danger signal in T lymphocytes. Cell Immunol 243(1):58–65

    Article  PubMed  CAS  Google Scholar 

  177. Aswad F, Kawamura H, Dennert G (2005) High sensitivity of CD4+ CD25+ regulatory T cells to extracellular metabolites nicotinamide adenine dinucleotide and ATP: a role for P2X7 receptors. J Immunol 175(5):3075–3083

    PubMed  CAS  Google Scholar 

  178. Jamieson GP, Snook MB, Thurlow PJ, Wiley JS (1996) Extracellular ATP causes of loss of l-selectin from human lymphocytes via occupancy of P2Z purinocepters. J Cell Physiol 166(3):637–642

    Article  PubMed  CAS  Google Scholar 

  179. Labasi JM, Petrushova N, Donovan C, McCurdy S, Lira P et al (2002) Absence of the P2X7 receptor alters leukocyte function and attenuates an inflammatory response. J Immunol 168(12):6436–6445

    PubMed  CAS  Google Scholar 

  180. Smalley DM, Ley K (2005) l-selectin: mechanisms and physiological significance of ectodomain cleavage. J Cell Mol Med 9(2):255–266

    Article  PubMed  CAS  Google Scholar 

  181. Baricordi OR, Melchiorri L, Adinolfi E, Falzoni S, Chiozzi P et al (1999) Increased proliferation rate of lymphoid cells transfected with the P2X(7) ATP receptor. J Biol Chem 274(47):33206–33208

    Article  PubMed  CAS  Google Scholar 

  182. Adinolfi E, Callegari MG, Ferrari D, Bolognesi C, Minelli M et al (2005) Basal activation of the P2X7 ATP receptor elevates mitochondrial calcium and potential, increases cellular ATP levels, and promotes serum-independent growth. Mol Biol Cell 16(7):3260–3272

    Article  PubMed  CAS  Google Scholar 

  183. Gorini S, Callegari G, Romagnoli G, Mammi C, Mavilio D et al (2010) ATP secreted by endothelial cells blocks CX(3)CL 1-elicited natural killer cell chemotaxis and cytotoxicity via P2Y(1)(1) receptor activation. Blood 116(22):4492–4500

    Article  PubMed  CAS  Google Scholar 

  184. Schmidt A, Ortaldo JR, Herberman RB (1984) Inhibition of human natural killer cell reactivity by exogenous adenosine 5′-triphosphate. J Immunol 132(1):146–150

    PubMed  CAS  Google Scholar 

  185. Dombrowski KE, Cone JC, Bjorndahl JM, Phillips CA (1995) Irreversible inhibition of human natural killer cell natural cytotoxicity by modification of the extracellular membrane by the adenine nucleotide analog 5′-p-(fluorosulfonyl)benzoyl adenosine. Cell Immunol 160(2):199–204

    Article  PubMed  CAS  Google Scholar 

  186. Krishnaraj R (1992) Negative modulation of human NK cell activity by purinoceptors. 1. Effect of exogenous adenosine triphosphate. Cell Immunol 141(2):306–322

    Article  PubMed  CAS  Google Scholar 

  187. Miller JS, Cervenka T, Lund J, Okazaki IJ, Moss J (1999) Purine metabolites suppress proliferation of human NK cells through a lineage-specific purine receptor. J Immunol 162(12):7376–7382

    PubMed  CAS  Google Scholar 

  188. Beldi G, Banz Y, Kroemer A, Sun X, Wu Y et al (2010) Deletion of CD39 on natural killer cells attenuates hepatic ischemia/reperfusion injury in mice. Hepatology 51(5):1702–1711

    Article  PubMed  CAS  Google Scholar 

  189. Hogan SP, Rosenberg HF, Moqbel R, Phipps S, Foster PS et al (2008) Eosinophils: biological properties and role in health and disease. Clin Exp Allergy 38(5):709–750

    Article  PubMed  CAS  Google Scholar 

  190. Burgers JA, Schweizer RC, Koenderman L, Bruijnzeel PL, Akkerman JW (1993) Human platelets secrete chemotactic activity for eosinophils. Blood 81(1):49–55

    PubMed  CAS  Google Scholar 

  191. Ferrari D, Idzko M, Dichmann S, Purlis D, Virchow C et al (2000) P2 purinergic receptors of human eosinophils: characterization and coupling to oxygen radical production. FEBS Lett 486(3):217–224

    Article  PubMed  CAS  Google Scholar 

  192. Idzko M, Dichmann S, Panther E, Ferrari D, Herouy Y et al (2001) Functional characterization of P2Y and P2X receptors in human eosinophils. J Cell Physiol 188(3):329–336

    Article  PubMed  CAS  Google Scholar 

  193. Vanderstocken G, Bondue B, Horckmans M, Di Pietrantonio L, Robaye B et al (2010) P2Y2 receptor regulates VCAM-1 membrane and soluble forms and eosinophil accumulation during lung inflammation. J Immunol 185(6):3702–3707

    Article  PubMed  CAS  Google Scholar 

  194. Dichmann S, Idzko M, Zimpfer U, Hofmann C, Ferrari D et al (2000) Adenosine triphosphate-induced oxygen radical production and CD11b up-regulation: Ca(++) mobilization and actin reorganization in human eosinophils. Blood 95(3):973–978

    PubMed  CAS  Google Scholar 

  195. Saito H, Ebisawa M, Reason DC, Ohno K, Kurihara K et al (1991) Extracellular ATP stimulates interleukin-dependent cultured mast cells and eosinophils through calcium mobilization. Int Arch Allergy Appl Immunol 94(1–4):68–70

    Article  PubMed  CAS  Google Scholar 

  196. Idzko M, Panther E, Bremer HC, Sorichter S, Luttmann W et al (2003) Stimulation of P2 purinergic receptors induces the release of eosinophil cationic protein and interleukin-8 from human eosinophils. Br J Pharmacol 138(7):1244–1250

    Article  PubMed  CAS  Google Scholar 

  197. Kobayashi T, Kouzaki H, Kita H (2010) Human eosinophils recognize endogenous danger signal crystalline uric acid and produce proinflammatory cytokines mediated by autocrine ATP. J Immunol 184(11):6350–6358

    Article  PubMed  CAS  Google Scholar 

  198. Uratsuji H, Tada Y, Kawashima T, Kamata M, Hau CS et al (2012) P2Y6 receptor signaling pathway mediates inflammatory responses induced by monosodium urate crystals. J Immunol 188(1):436–444

    Article  PubMed  CAS  Google Scholar 

  199. Jaffar ZH, Pearce FL (1993) Some characteristics of the ATP-induced histamine release from and permeabilization of rat mast cells. Agents Actions 40(1–2):18–27

    Article  PubMed  CAS  Google Scholar 

  200. Schulman ES, Glaum MC, Post T, Wang Y, Raible DG et al (1999) ATP modulates anti-IgE-induced release of histamine from human lung mast cells. Am J Respir Cell Mol Biol 20(3):530–537

    Article  PubMed  CAS  Google Scholar 

  201. Dahlquist R, Diamant B (1970) Further observations on ATP-induced histamine release from rat mast cells. Acta Pharmacol Toxicol (Copenh) 28(1):43

    CAS  Google Scholar 

  202. Dahlquist R (1974) Relationship of uptake of sodium and 45calcium to ATP-induced histamine release from rat mast cells. Acta Pharmacol Toxicol (Copenh) 35(1):11–22

    Article  CAS  Google Scholar 

  203. Diamant B (1967) The mechanism of histamine release from rat mast cells induced by adenosine triphosphate. Acta Pharmacol Toxicol (Copenh) 25(S4):33

    Google Scholar 

  204. Kruger PG, Diamant B, Dahlquist R (1974) Morphological changes induced by ATP on rat mast cells and their relationship to histamine release. Int Arch Allergy Appl Immunol 46(5):676–688

    Article  PubMed  CAS  Google Scholar 

  205. Bennett JP, Cockcroft S, Gomperts BD (1981) Rat mast cells permeabilized with ATP secrete histamine in response to calcium ions buffered in the micromolar range. J Physiol 317:335–345

    PubMed  CAS  Google Scholar 

  206. Cockcroft S, Gomperts BD (1979) ATP induces nucleotide permeability in rat mast cells. Nature 279(5713):541–542

    Article  PubMed  CAS  Google Scholar 

  207. Cockcroft S, Gomperts BD (1979) Activation and inhibition of calcium-dependent histamine secretion by ATP ions applied to rat mast cells. J Physiol 296:229–243

    PubMed  CAS  Google Scholar 

  208. Peterson C (1974) Histamine release induced by compound 48–80 from isolated rat cells: dependence on endogenous ATP. Acta Pharmacol Toxicol (Copenh) 34(5):356–367

    Article  CAS  Google Scholar 

  209. Johansen T, Chakravarty N (1972) Dependence of histamine release from rat mast cells on adenosine triphosphate. Naunyn Schmiedebergs Arch Pharmacol 275(4):457–463

    Article  PubMed  CAS  Google Scholar 

  210. Johansen T (1980) Further observations on the utilization of adenosine triphosphate in rat mast cells during histamine release induced by the ionophore A23187. Br J Pharmacol 69(4):657–662

    Article  PubMed  CAS  Google Scholar 

  211. Peterson C, Diamant B (1973) Utilization of endogenous ATP during histamine release from isolated rat mast cells. Agents Actions 3(3):189–190

    Article  PubMed  CAS  Google Scholar 

  212. Diamant B, Kruger PG (1967) Histamine release from isolated rat peritoneal mast cells induced by adenosine-5′-triphosphate. Acta Physiol Scand 71(4):291–302

    Article  PubMed  CAS  Google Scholar 

  213. Bradding P, Okayama Y, Kambe N, Saito H (2003) Ion channel gene expression in human lung, skin, and cord blood-derived mast cells. J Leukoc Biol 73(5):614–620

    Article  PubMed  CAS  Google Scholar 

  214. Wareham K, Vial C, Wykes RC, Bradding P, Seward EP (2009) Functional evidence for the expression of P2X1, P2X4 and P2X7 receptors in human lung mast cells. Br J Pharmacol 157(7):1215–1224

    Article  PubMed  CAS  Google Scholar 

  215. Gao ZG, Ding Y, Jacobson KA (2010) UDP-glucose acting at P2Y14 receptors is a mediator of mast cell degranulation. Biochem Pharmacol 79(6):873–879

    Article  PubMed  CAS  Google Scholar 

  216. Gao ZG, Wei Q, Jayasekara MP, Jacobson KA (2012) The role of P2Y(14) and other P2Y receptors in degranulation of human LAD2 mast cells. Purinergic Signal

  217. Dahlquist R, Diamant B (1974) Interaction of ATP and calcium on the rat mast cell: effect on histamine release. Acta Pharmacol Toxicol (Copenh) 34(5):368–384

    Article  CAS  Google Scholar 

  218. Qian YX, McCloskey MA (1993) Activation of mast cell K+ channels through multiple G protein-linked receptors. Proc Natl Acad Sci U S A 90(16):7844–7848

    Article  PubMed  CAS  Google Scholar 

  219. Tatham PE, Lindau M (1990) ATP-induced pore formation in the plasma membrane of rat peritoneal mast cells. J Gen Physiol 95(3):459–476

    Article  PubMed  CAS  Google Scholar 

  220. Sudo N, Tanaka K, Koga Y, Okumura Y, Kubo C et al (1996) Extracellular ATP activates mast cells via a mechanism that is different from the activation induced by the cross-linking of Fc receptors. J Immunol 156(10):3970–3979

    PubMed  CAS  Google Scholar 

  221. Gao ZG, Ding Y, Jacobson KA (2010) P2Y(13) receptor is responsible for ADP-mediated degranulation in RBL-2H3 rat mast cells. Pharmacol Res 62(6):500–505

    Article  PubMed  CAS  Google Scholar 

  222. Bulanova E, Bulfone-Paus S (2010) P2 receptor-mediated signaling in mast cell biology. Purinergic Signal 6(1):3–17

    Article  PubMed  CAS  Google Scholar 

  223. Osipchuk Y, Cahalan M (1992) Cell-to-cell spread of calcium signals mediated by ATP receptors in mast cells. Nature 359(6392):241–244

    Article  PubMed  CAS  Google Scholar 

  224. Carroll WA, Donnelly-Roberts D, Jarvis MF (2009) Selective P2X(7) receptor antagonists for chronic inflammation and pain. Purinergic Signal 5(1):63–73

    Article  PubMed  CAS  Google Scholar 

  225. Romagnoli R, Baraldi PG, Cruz-Lopez O, Lopez-Cara C, Preti D et al (2008) The P2X7 receptor as a therapeutic target. Expert Opin Ther Targets 12(5):647–661

    Article  PubMed  CAS  Google Scholar 

  226. Arulkumaran N, Unwin RJ, Tam FW (2011) A potential therapeutic role for P2X7 receptor (P2X7R) antagonists in the treatment of inflammatory diseases. Expert Opin Investig Drugs 20(7):897–915

    Article  PubMed  CAS  Google Scholar 

  227. Accurso FJ, Moss RB, Wilmott RW, Anbar RD, Schaberg AE et al (2011) Denufosol tetrasodium in patients with cystic fibrosis and normal to mildly impaired lung function. Am J Respir Crit Care Med 183(5):627–634

    Article  PubMed  CAS  Google Scholar 

  228. Burnstock G (2006) Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol Rev 58(1):58–86

    Article  PubMed  CAS  Google Scholar 

  229. Cattaneo M (2007) Platelet P2 receptors: old and new targets for antithrombotic drugs. Expert Rev Cardiovasc Ther 5(1):45–55

    Article  PubMed  CAS  Google Scholar 

  230. White N, Burnstock G (2006) P2 receptors and cancer. Trends Pharmacol Sci 27(4):211–217

    Article  PubMed  CAS  Google Scholar 

  231. Di Virgilio F (2012) Purines, purinergic receptors, and cancer. Cancer Res 72(21):5441–5447

    Article  PubMed  CAS  Google Scholar 

  232. Nakamura M, Imanaka T, Sakamoto A (2012) Diquafosol ophthalmic solution for dry eye treatment. Adv Ther 29(7):579–589

    Article  PubMed  CAS  Google Scholar 

  233. Ford AP, Gever JR, Nunn PA, Zhong Y, Cefalu JS et al (2006) Purinoceptors as therapeutic targets for lower urinary tract dysfunction. Br J Pharmacol 147(Suppl 2):S132–S143

    Article  PubMed  CAS  Google Scholar 

  234. Cattaneo M (2010) New P2Y(12) inhibitors. Circulation 121(1):171–179

    Article  PubMed  Google Scholar 

  235. Wartak SA, Lotfi A, Rothberg M (2009) Ticagrelor versus clopidogrel in acute coronary syndromes. N Engl J Med 361(24):2386–2387

    PubMed  CAS  Google Scholar 

  236. Gum RJ, Wakefield B, Jarvis MF (2012) P2X receptor antagonists for pain management: examination of binding and physicochemical properties. Purinergic Signal 8(Suppl 1):41–56

    Article  PubMed  CAS  Google Scholar 

  237. Jacobson KA, Boeynaems JM (2010) P2Y nucleotide receptors: promise of therapeutic applications. Drug Discov Today 15(13–14):570–578

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by funding from The Research Foundation Flanders (FWO); research project Nr. G.0641.10 to KVC, and a Concerted Research Action project (01G01009) from the Special Research Fund of Ghent University. The figures were generated using Servier Medical Art’s Powerpoint image banks available at www.servier.com.

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Correspondence to Koen Van Crombruggen.

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Fenila Jacob and Koen Van Crombruggen contributed equally to this work

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Jacob, F., Novo, C.P., Bachert, C. et al. Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses. Purinergic Signalling 9, 285–306 (2013). https://doi.org/10.1007/s11302-013-9357-4

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  • DOI: https://doi.org/10.1007/s11302-013-9357-4

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