Skip to main content

Advertisement

SpringerLink
Log in

Involvement of P2 receptors in hematopoiesis and hematopoietic disorders, and as pharmacological targets

  • Review Article
  • Published:
Purinergic Signalling Aims and scope Submit manuscript

Abstract

Several reports have shown the presence of P2 receptors in hematopoietic stem cells (HSCs). These receptors are activated by extracellular nucleotides released from different sources. In the hematopoietic niche, the release of purines and pyrimidines in the milieu by lytic and nonlytic mechanisms has been described. The expression of P2 receptors from HSCs until maturity is still intriguing scientists. Several reports have shown the participation of P2 receptors in events associated with modulation of the immune system, but their participation in other physiological processes is under investigation. The presence of P2 receptors in HSCs and their ability to modulate this population have awakened interest in exploring the involvement of P2 receptors in hematopoiesis and their participation in hematopoietic disorders. Among the P2 receptors, the receptor P2X7 is of particular interest, because of its different roles in hematopoietic cells (e.g., infection, inflammation, cell death and survival, leukemias and lymphomas), making the P2X7 receptor a promising pharmacological target. Additionally, the role of P2Y12 receptor in platelet activation has been well-documented and is the main example of the importance of the pharmacological modulation of P2 receptor activity. In this review, we focus on the role of P2 receptors in the hematopoietic system, addressing these receptors as potential pharmacological targets.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Schwiebert EM, Zsembery A (2003) Extracellular ATP as a signaling molecule for epithelial cells. Biochim Biophys Acta 1615(1-2):7–32. https://doi.org/10.1016/S0005-2736(03)00210-4

    Article  CAS  PubMed  Google Scholar 

  2. Cockcroft S, Gomperts BD (1979) Activation and inhibition of calcium-dependent histamine secretion by ATP ions applied to rat mast cells. J Physiol:296229–296243. https://doi.org/10.1113/jphysiol.1979.sp013002

  3. Lazarowski ER (2012) Vesicular and conductive mechanisms of nucleotide release. Purinergic Signal 8(3):359–373. https://doi.org/10.1007/s11302-012-9304-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Burnstock G, Dumsday B, Smythe A (1972) Atropine resistant excitation of the urinary bladder: the possibility of transmission via nerves releasing a purine nucleotide. Br J Pharmacol 44(3):451–461

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Lim To WK, Kumar P, Marshall JM (2015) Hypoxia is an effective stimulus for vesicular release of ATP from human umbilical vein endothelial cells. Placenta 36(7):759–766. https://doi.org/10.1016/j.placenta.2015.04.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Orriss IR, Knight GE, Utting JC, Taylor SE, Burnstock G, Arnett TR (2009) Hypoxia stimulates vesicular ATP release from rat osteoblasts. J Cell Physiol 220(1):155–162. https://doi.org/10.1002/jcp.21745

    Article  CAS  PubMed  Google Scholar 

  7. Hayton MJ, Dillon JP, Glynn D, Curran JM, Gallagher JA, Buckley KA (2005) Involvement of adenosine 5′-triphosphate in ultrasound-induced fracture repair. Ultrasound Med Biol 31(8):1131–1138. https://doi.org/10.1016/j.ultrasmedbio.2005.04.017

    Article  PubMed  Google Scholar 

  8. Alvarenga EC, Rodrigues R, Caricati-Neto A, Silva-Filho FC, Paredes-Gamero EJ, Ferreira AT (2010) Low-intensity pulsed ultrasound-dependent osteoblast proliferation occurs by via activation of the P2Y receptor: role of the P2Y1 receptor. Bone 46(2):355–362. https://doi.org/10.1016/j.bone.2009.09.017

    Article  CAS  PubMed  Google Scholar 

  9. Locovei S, Wang J, Dahl G (2006) Activation of pannexin 1 channels by ATP through P2Y receptors and by cytoplasmic calcium. FEBS Lett 580(1):239–244. https://doi.org/10.1016/j.febslet.2005.12.004

    Article  CAS  PubMed  Google Scholar 

  10. Penuela S, Gehi R, Laird DW (2013) The biochemistry and function of pannexin channels. Biochim Biophys Acta 1828(1):15–22. https://doi.org/10.1016/j.bbamem.2012.01.017

    Article  CAS  PubMed  Google Scholar 

  11. Miteva AS, Gaydukov AE, Shestopalov VI, Balezina OP (2018) Mechanism of P2X7 receptor-dependent enhancement of neuromuscular transmission in pannexin 1 knockout mice. Purinergic Signal 14(4):459–469. https://doi.org/10.1007/s11302-018-9630-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cotrina ML, Lin JH, Alves-Rodrigues A, Liu S, Li J, Azmi-Ghadimi H, Kang J, Naus CC, Nedergaard M (1998) Connexins regulate calcium signaling by controlling ATP release. Proc Natl Acad Sci U S A 95(26):15735–15740

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Kang J, Kang N, Lovatt D, Torres A, Zhao Z, Lin J, Nedergaard M (2008) Connexin 43 hemichannels are permeable to ATP. J Neurosci 28(18):4702–4711. https://doi.org/10.1523/JNEUROSCI.5048-07.2008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ledderose C, Bao Y, Zhang J, Junger WG (2015) Novel method for real-time monitoring of ATP release reveals multiple phases of autocrine purinergic signalling during immune cell activation. Acta Physiol (Oxf) 213(2):334–345. https://doi.org/10.1111/apha.12435

    Article  CAS  Google Scholar 

  15. Harada Y, Kato Y, Miyaji T, Omote H, Moriyama Y, Hiasa M (2018) Vesicular nucleotide transporter mediates ATP release and migration in neutrophils. J Biol Chem 293(10):3770–3779. https://doi.org/10.1074/jbc.M117.810168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Locovei S, Bao L, Dahl G (2006) Pannexin 1 in erythrocytes: function without a gap. Proc Natl Acad Sci U S A 103(20):7655–7659. https://doi.org/10.1073/pnas.0601037103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ransford GA, Fregien N, Qiu F, Dahl G, Conner GE, Salathe M (2009) Pannexin 1 contributes to ATP release in airway epithelia. Am J Respir Cell Mol Biol 41(5):525–534. https://doi.org/10.1165/rcmb.2008-0367OC

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gatof D, Kilic G, Fitz JG (2004) Vesicular exocytosis contributes to volume-sensitive ATP release in biliary cells. Am J Physiol Gastrointest Liver Physiol 286(4):G538–G546. https://doi.org/10.1152/ajpgi.00355.2003

    Article  CAS  PubMed  Google Scholar 

  19. Kaczmarek-Hajek K, Lorinczi E, Hausmann R, Nicke A (2012) Molecular and functional properties of P2X receptors--recent progress and persisting challenges. Purinergic Signal 8(3):375–417. https://doi.org/10.1007/s11302-012-9314-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Alves LA, da Silva JH, Ferreira DN, Fidalgo-Neto AA, Teixeira PC, de Souza CA, Caffarena ER, de Freitas MS (2014) Structural and molecular modeling features of P2X receptors. Int J Mol Sci 15(3):4531–4549. https://doi.org/10.3390/ijms15034531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Rokic MB, Stojilkovic SS (2013) Two open states of P2X receptor channels. Front Cell Neurosci 7215. https://doi.org/10.3389/fncel.2013.00215

  22. Di Virgilio F, Sarti AC, Falzoni S, De Marchi E, Adinolfi E (2018) Extracellular ATP and P2 purinergic signalling in the tumour microenvironment. Nat Rev Cancer 18(10):601–618. https://doi.org/10.1038/s41568-018-0037-0

    Article  CAS  PubMed  Google Scholar 

  23. North RA (2016) P2X receptors. Philos Trans R Soc Lond B Biol Sci 371(1700). https://doi.org/10.1098/rstb.2015.0427

  24. Nicke A, Baumert HG, Rettinger J, Eichele A, Lambrecht G, Mutschler E, Schmalzing G (1998) P2X1 and P2X3 receptors form stable trimers: a novel structural motif of ligand-gated ion channels. EMBO J 17(11):3016–3028. https://doi.org/10.1093/emboj/17.11.3016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Stelmashenko O, Lalo U, Yang Y, Bragg L, North RA, Compan V (2012) Activation of trimeric P2X2 receptors by fewer than three ATP molecules. Mol Pharmacol 82(4):760–766. https://doi.org/10.1124/mol.112.080903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Evans RJ (2009) Orthosteric and allosteric binding sites of P2X receptors. Eur Biophys J 38(3):319–327. https://doi.org/10.1007/s00249-008-0275-2

    Article  CAS  PubMed  Google Scholar 

  27. Coddou C, Acuna-Castillo C, Bull P, Huidobro-Toro JP (2007) Dissecting the facilitator and inhibitor allosteric metal sites of the P2X4 receptor channel: critical roles of CYS132 for zinc potentiation and ASP138 for copper inhibition. J Biol Chem 282(51):36879–36886. https://doi.org/10.1074/jbc.M706925200

    Article  CAS  PubMed  Google Scholar 

  28. Hou Z, Cao J (2016) Comparative study of the P2X gene family in animals and plants. Purinergic Signal 12(2):269–281. https://doi.org/10.1007/s11302-016-9501-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Valera S, Hussy N, Evans RJ, Adami N, North RA, Surprenant A, Buell G (1994) A new class of ligand-gated ion channel defined by P2x receptor for extracellular ATP. Nature 371(6497):516–519. https://doi.org/10.1038/371516a0

    Article  CAS  PubMed  Google Scholar 

  30. Evans RJ, Lewis C, Buell G, Valera S, North RA, Surprenant A (1995) Pharmacological characterization of heterologously expressed ATP-gated cation channels (P2x purinoceptors). Mol Pharmacol 48(2):178–183

    CAS  PubMed  Google Scholar 

  31. Savi P, Bornia J, Salel V, Delfaud M, Herbert JM (1997) Characterization of P2x1 purinoreceptors on rat platelets: effect of clopidogrel. Br J Haematol 98(4):880–886

    CAS  PubMed  Google Scholar 

  32. Brake AJ, Wagenbach MJ, Julius D (1994) New structural motif for ligand-gated ion channels defined by an ionotropic ATP receptor. Nature 371(6497):519–523. https://doi.org/10.1038/371519a0

    Article  CAS  PubMed  Google Scholar 

  33. Surprenant A, Buell G, North RA (1995) P2X receptors bring new structure to ligand-gated ion channels. Trends Neurosci 18(5):224–229

    CAS  PubMed  Google Scholar 

  34. Chen CC, Akopian AN, Sivilotti L, Colquhoun D, Burnstock G, Wood JN (1995) A P2X purinoceptor expressed by a subset of sensory neurons. Nature 377(6548):428–431. https://doi.org/10.1038/377428a0

    Article  CAS  PubMed  Google Scholar 

  35. Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50(3):413–492

    CAS  PubMed  Google Scholar 

  36. Soto F, Lambrecht G, Nickel P, Stuhmer W, Busch AE (1999) Antagonistic properties of the suramin analogue NF023 at heterologously expressed P2X receptors. Neuropharmacology 38(1):141–149

    CAS  PubMed  Google Scholar 

  37. Turner CM, Vonend O, Chan C, Burnstock G, Unwin RJ (2003) The pattern of distribution of selected ATP-sensitive P2 receptor subtypes in normal rat kidney: an immunohistological study. Cells Tissues Organs 175(2):105–117. https://doi.org/10.1159/000073754

    Article  CAS  PubMed  Google Scholar 

  38. Padilla K, Gonzalez-Mendoza D, Berumen LC, Escobar JE, Miledi R, Garcia-Alcocer G (2016) Differential gene expression patterns and colocalization of ATP-gated P2X6/P2X4 ion channels during rat small intestine ontogeny. Gene Expr Patterns 21(2):81–88. https://doi.org/10.1016/j.gep.2016.08.002

    Article  CAS  PubMed  Google Scholar 

  39. Tian M, Abdelrahman A, Weinhausen S, Hinz S, Weyer S, Dosa S, El-Tayeb A, Muller CE (2014) Carbamazepine derivatives with P2X4 receptor-blocking activity. Bioorg Med Chem 22(3):1077–1088. https://doi.org/10.1016/j.bmc.2013.12.035

    Article  CAS  PubMed  Google Scholar 

  40. Torres GE, Haines WR, Egan TM, Voigt MM (1998) Co-expression of P2X1 and P2X5 receptor subunits reveals a novel ATP-gated ion channel. Mol Pharmacol 54(6):989–993

    CAS  PubMed  Google Scholar 

  41. Haines WR, Torres GE, Voigt MM, Egan TM (1999) Properties of the novel ATP-gated ionotropic receptor composed of the P2X(1) and P2X(5) isoforms. Mol Pharmacol 56(4):720–727

    CAS  PubMed  Google Scholar 

  42. Collo G, North RA, Kawashima E, Merlo-Pich E, Neidhart S, Surprenant A, Buell G (1996) Cloning OF P2X5 and P2X6 receptors and the distribution and properties of an extended family of ATP-gated ion channels. J Neurosci 16(8):2495–2507

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Barrera NP, Ormond SJ, Henderson RM, Murrell-Lagnado RD, Edwardson JM (2005) Atomic force microscopy imaging demonstrates that P2X2 receptors are trimers but that P2X6 receptor subunits do not oligomerize. J Biol Chem 280(11):10759–10765. https://doi.org/10.1074/jbc.M412265200

    Article  CAS  PubMed  Google Scholar 

  44. Di Virgilio F, Chiozzi P, Ferrari D, Falzoni S, Sanz JM, Morelli A, Torboli M, Bolognesi G, Baricordi OR (2001) Nucleotide receptors: an emerging family of regulatory molecules in blood cells. Blood 97(3):587–600

    PubMed  Google Scholar 

  45. Schulze-Lohoff E, Hugo C, Rost S, Arnold S, Gruber A, Brune B, Sterzel RB (1998) Extracellular ATP causes apoptosis and necrosis of cultured mesangial cells via P2Z/P2X7 receptors. Am J Physiol 275(6):F962–F971. https://doi.org/10.1152/ajprenal.1998.275.6.F962

    Article  CAS  PubMed  Google Scholar 

  46. Paredes-Gamero EJ, Dreyfuss JL, Nader HB, Miyamoto Oshiro ME, Ferreira AT (2007) P2X7-induced apoptosis decreases by aging in mice myeloblasts. Exp Gerontol 42(4):320–326. https://doi.org/10.1016/j.exger.2006.11.011

    Article  CAS  PubMed  Google Scholar 

  47. Paredes-Gamero EJ, Franca JP, Moraes AA, Aguilar MO, Oshiro ME, Ferreira AT (2004) Problems caused by high concentration of ATP on activation of the P2X7 receptor in bone marrow cells loaded with the Ca2+ fluorophore fura-2. J Fluoresc 14(6):711–722

    CAS  PubMed  Google Scholar 

  48. Fischer W, Urban N, Immig K, Franke H, Schaefer M (2014) Natural compounds with P2X7 receptor-modulating properties. Purinergic Signal 10(2):313–326. https://doi.org/10.1007/s11302-013-9392-1

    Article  CAS  PubMed  Google Scholar 

  49. Murgia M, Hanau S, Pizzo P, Rippa M, Di Virgilio F (1993) Oxidized ATP. An irreversible inhibitor of the macrophage purinergic P2Z receptor. J Biol Chem 268(11):8199–8203

    CAS  PubMed  Google Scholar 

  50. Gargett CE, Wiley JS (1997) The isoquinoline derivative KN-62 a potent antagonist of the P2Z-receptor of human lymphocytes. Br J Pharmacol 120(8):1483–1490. https://doi.org/10.1038/sj.bjp.0701081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Beigi RD, Kertesy SB, Aquilina G, Dubyak GR (2003) Oxidized ATP (oATP) attenuates proinflammatory signaling via P2 receptor-independent mechanisms. Br J Pharmacol 140(3):507–519. https://doi.org/10.1038/sj.bjp.0705470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Bin Dayel A, Evans RJ, Schmid R (2019) Mapping the site of action of human P2X7 receptor antagonists AZ11645373, Brilliant Blue G, KN-62, Calmidazolium, and ZINC58368839 to the intersubunit allosteric pocket. Mol Pharmacol 96(3):355–363. https://doi.org/10.1124/mol.119.116715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. De Marchi E, Orioli E, Pegoraro A, Sangaletti S, Portararo P, Curti A, Colombo MP, Di Virgilio F, Adinolfi E (2019) The P2X7 receptor modulates immune cells infiltration, ectonucleotidases expression and extracellular ATP levels in the tumor microenvironment. Oncogene 38(19):3636–3650. https://doi.org/10.1038/s41388-019-0684-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Danquah W, Meyer-Schwesinger C, Rissiek B, Pinto C, Serracant-Prat A, Amadi M, Iacenda D, Knop JH, Hammel A, Bergmann P, Schwarz N, Assuncao J, Rotthier W, Haag F, Tolosa E, Bannas P, Boue-Grabot E, Magnus T, Laeremans T, Stortelers C, Koch-Nolte F (2016) Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation. Sci Transl Med 8(366):366ra162. https://doi.org/10.1126/scitranslmed.aaf8463

    Article  CAS  PubMed  Google Scholar 

  55. von Kugelgen I (2019) Pharmacology of P2Y receptors. Brain Res Bull:15112–15124. https://doi.org/10.1016/j.brainresbull.2019.03.010

  56. Niss Arfelt K, Fares S, Sparre-Ulrich AH, Hjorto GM, Gasbjerg LS, Molleskov-Jensen AS, Benned-Jensen T, Rosenkilde MM (2017) Signaling via G proteins mediates tumorigenic effects of GPR87. Cell Signal:309–318. https://doi.org/10.1016/j.cellsig.2016.11.009

  57. Webb TE, Simon J, Krishek BJ, Bateson AN, Smart TG, King BF, Burnstock G, Barnard EA (1993) Cloning and functional expression of a brain G-protein-coupled ATP receptor. FEBS Lett 324(2):219–225

    CAS  PubMed  Google Scholar 

  58. Marteau F, Le Poul E, Communi D, Labouret C, Savi P, Boeynaems JM, Gonzalez NS (2003) Pharmacological characterization of the human P2Y13 receptor. Mol Pharmacol 64(1):104–112. https://doi.org/10.1124/mol.64.1.104

    Article  CAS  PubMed  Google Scholar 

  59. Turner NA, Moake JL, McIntire LV (2001) Blockade of adenosine diphosphate receptors P2Y(12) and P2Y(1) is required to inhibit platelet aggregation in whole blood under flow. Blood 98(12):3340–3345

    CAS  PubMed  Google Scholar 

  60. Erb L, Lustig KD, Sullivan DM, Turner JT, Weisman GA (1993) Functional expression and photoaffinity labeling of a cloned P2U purinergic receptor. Proc Natl Acad Sci U S A 90(22):10449–10453

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Communi D, Motte S, Boeynaems JM, Pirotton S (1996) Pharmacological characterization of the human P2Y4 receptor. Eur J Pharmacol 317(2-3):383–389

    CAS  PubMed  Google Scholar 

  62. Freeman K, Tsui P, Moore D, Emson PC, Vawter L, Naheed S, Lane P, Bawagan H, Herrity N, Murphy K, Sarau HM, Ames RS, Wilson S, Livi GP, Chambers JK (2001) Cloning, pharmacology, and tissue distribution of G-protein-coupled receptor GPR105 (KIAA0001) rodent orthologs. Genomics 78(3):124–128 https://doi.org/10.1006/geno.2001.6662

    CAS  PubMed  Google Scholar 

  63. Cockcroft S, Gomperts BD (1980) The ATP4- receptor of rat mast cells. Biochem J 188(3):789–798

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  65. Naumov AP, Kuryshev YA, Kaznacheyeva EV, Mozhayeva GN (1992) ATP-activated Ca(2+)-permeable channels in rat peritoneal macrophages. FEBS Lett 313(3):285–287

    CAS  PubMed  Google Scholar 

  66. Nuttle LC, Dubyak GR (1994) Differential activation of cation channels and non-selective pores by macrophage P2z purinergic receptors expressed in Xenopus oocytes. J Biol Chem 269(19):13988–13996

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  68. 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. https://doi.org/10.1067/mai.2001.114658

    Article  CAS  PubMed  Google Scholar 

  69. Idzko M, Dichmann S, Panther E, Ferrari D, Herouy Y, Virchow C Jr, Luttmann W, Di Virgilio F, Norgauer J (2001) Functional characterization of P2Y and P2X receptors in human eosinophils. J Cell Physiol 188(3):329–336. https://doi.org/10.1002/jcp.1129

    Article  CAS  PubMed  Google Scholar 

  70. Muller T, Robaye B, Vieira RP, Ferrari D, Grimm M, Jakob T, Martin SF, Di Virgilio F, Boeynaems JM, Virchow JC, Idzko M (2010) The purinergic receptor P2Y2 receptor mediates chemotaxis of dendritic cells and eosinophils in allergic lung inflammation. Allergy 65(12):1545–1553. https://doi.org/10.1111/j.1398-9995.2010.02426.x

    Article  CAS  PubMed  Google Scholar 

  71. Csoka B, Nemeth ZH, Szabo I, Davies DL, Varga ZV, Paloczi J, Falzoni S, Di Virgilio F, Muramatsu R, Yamashita T, Pacher P, Hasko G (2018) Macrophage P2X4 receptors augment bacterial killing and protect against sepsis. JCI Insight 3(11). https://doi.org/10.1172/jci.insight.9943199431

  72. Csoka B, Nemeth ZH, Toro G, Idzko M, Zech A, Koscso B, Spolarics Z, Antonioli L, Cseri K, Erdelyi K, Pacher P, Hasko G (2015) Extracellular ATP protects against sepsis through macrophage P2X7 purinergic receptors by enhancing intracellular bacterial killing. FASEB J 29(9):3626–3637. https://doi.org/10.1096/fj.15-272450fj.15-272450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Balazovich KJ, Boxer LA (1990) Extracellular adenosine nucleotides stimulate protein kinase C activity and human neutrophil activation. J Immunol 144(2):631–637

    CAS  PubMed  Google Scholar 

  74. 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

    CAS  PubMed  Google Scholar 

  75. Lecut C, Faccinetto C, Delierneux C, van Oerle R, Spronk HM, Evans RJ, El Benna J, Bours V, Oury C (2012) ATP-gated P2X1 ion channels protect against endotoxemia by dampening neutrophil activation. J Thromb Haemost 10(3):453–465. https://doi.org/10.1111/j.1538-7836.2011.04606.x

    Article  CAS  PubMed  Google Scholar 

  76. Maitre B, Magnenat S, Heim V, Ravanat C, Evans RJ, de la Salle H, Gachet C, Hechler B (2015) The P2X1 receptor is required for neutrophil extravasation during lipopolysaccharide-induced lethal endotoxemia in mice. J Immunol 194(2):739–749. https://doi.org/10.4049/jimmunol.1401786

    Article  CAS  PubMed  Google Scholar 

  77. Ribeiro-Filho AC, Buri MV, Barros CC, Dreyfuss JL, Nader HB, Justo GZ, Craveiro RB, Pesquero JB, Miranda A, Ferreira AT, Paredes-Gamero EJ (2016) Functional and molecular evidence for heteromeric association of P2Y1 receptor with P2Y2 and P2Y4 receptors in mouse granulocytes. BMC Pharmacol Toxicol 17(1):29. https://doi.org/10.1186/s40360-016-0072-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Leal Denis MF, Alvarez HA, Lauri N, Alvarez CL, Chara O, Schwarzbaum PJ (2016) Dynamic Regulation of Cell Volume and Extracellular ATP of Human Erythrocytes. PLoS One 11(6):e0158305. https://doi.org/10.1371/journal.pone.0158305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Vaziri C, Downes CP (1992) G-protein-mediated activation of turkey erythrocyte phospholipase C by beta-adrenergic and P2y-purinergic receptors. Biochem J 284(Pt 3):917–922

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Light DB, Attwood AJ, Siegel C, Baumann NL (2003) Cell swelling increases intracellular calcium in Necturus erythrocytes. J Cell Sci 116(Pt 1):101–109

    CAS  PubMed  Google Scholar 

  81. Hoffman JF, Dodson A, Wickrema A, Dib-Hajj SD (2004) Tetrodotoxin-sensitive Na+ channels and muscarinic and purinergic receptors identified in human erythroid progenitor cells and red blood cell ghosts. Proc Natl Acad Sci U S A 101(33):12370–12374. https://doi.org/10.1073/pnas.0404228101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Sluyter R, Shemon AN, Barden JA, Wiley JS (2004) Extracellular ATP increases cation fluxes in human erythrocytes by activation of the P2X7 receptor. J Biol Chem 279(43):44749–44755. https://doi.org/10.1074/jbc.M405631200

    Article  CAS  PubMed  Google Scholar 

  83. Paredes-Gamero EJ, Craveiro RB, Pesquero JB, Franca JP, Oshiro ME, Ferreira AT (2006) Activation of P2Y1 receptor triggers two calcium signaling pathways in bone marrow erythroblasts. Eur J Pharmacol 534(1-3):30–38. https://doi.org/10.1016/j.ejphar.2006.01.010

    Article  CAS  PubMed  Google Scholar 

  84. Burnstock G (2015) Blood cells: an historical account of the roles of purinergic signalling. Purinergic Signal 11(4):411–434 https://doi.org/10.1007/s11302-015-9462-7

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Di Virgilio F, Vuerich M (2015) Purinergic signaling in the immune system. Auton Neurosci:191117–191123. https://doi.org/10.1016/j.autneu.2015.04.011

  86. Rossi L, Salvestrini V, Ferrari D, Di Virgilio F, Lemoli RM (2012) The sixth sense: hematopoietic stem cells detect danger through purinergic signaling. Blood 120(12):2365–2375. https://doi.org/10.1182/blood-2012-04-422378

    Article  CAS  PubMed  Google Scholar 

  87. Ma Y, Adjemian S, Mattarollo SR, Yamazaki T, Aymeric L, Yang H, Portela Catani JP, Hannani D, Duret H, Steegh K, Martins I, Schlemmer F, Michaud M, Kepp O, Sukkurwala AQ, Menger L, Vacchelli E, Droin N, Galluzzi L, Krzysiek R, Gordon S, Taylor PR, Van Endert P, Solary E, Smyth MJ, Zitvogel L, Kroemer G (2013) Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity 38(4):729–741. https://doi.org/10.1016/j.immuni.2013.03.003

    Article  CAS  PubMed  Google Scholar 

  88. Vieira JM, Gutierres JM, Carvalho FB, Stefanello N, Oliveira L, Cardoso AM, Morsch VM, Pillat MM, Ulrich H, Duarte MMF, Schetinger MRC, Spanevello RM (2018) Caffeine and high intensity exercise: Impact on purinergic and cholinergic signalling in lymphocytes and on cytokine levels. Biomed Pharmacother:1081731–1081738. https://doi.org/10.1016/j.biopha.2018.10.006

  89. Savio LEB, de Andrade MP, da Silva CG, Coutinho-Silva R (2018) The P2X7 Receptor in Inflammatory Diseases: angel or Demon? Front Pharmacol 952. https://doi.org/10.3389/fphar.2018.00052

  90. Granata S, Masola V, Zoratti E, Scupoli MT, Baruzzi A, Messa M, Sallustio F, Gesualdo L, Lupo A, Zaza G (2015) NLRP3 inflammasome activation in dialyzed chronic kidney disease patients. PLoS One 10(3):e0122272. https://doi.org/10.1371/journal.pone.0122272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Schenk U, Frascoli M, Proietti M, Geffers R, Traggiai E, Buer J, Ricordi C, Westendorf AM, Grassi F (2011) ATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors. Sci Signal 4(162):ra12. https://doi.org/10.1126/scisignal.2001270

    Article  PubMed  Google Scholar 

  92. Soehnlein O, Lindbom L (2010) Phagocyte partnership during the onset and resolution of inflammation. Nat Rev Immunol 10(6):427–439. https://doi.org/10.1038/nri2779

    Article  CAS  PubMed  Google Scholar 

  93. Gutteridge JMC, Halliwell B (2018) Mini-review: oxidative stress, redox stress or redox success? Biochem Biophys Res Commun 502(2):183–186. https://doi.org/10.1016/j.bbrc.2018.05.045

    Article  CAS  PubMed  Google Scholar 

  94. Munoz FM, Gao R, Tian Y, Henstenburg BA, Barrett JE, Hu H (2017) Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice. Sci Rep 7(1):3539. https://doi.org/10.1038/s41598-017-03813-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Kawano A, Hayakawa A, Kojima S, Tsukimoto M, Sakamoto H (2015) Purinergic signaling mediates oxidative stress in UVA-exposed THP-1 cells. Toxicol Rep:2391–2400. https://doi.org/10.1016/j.toxrep.2015.01.015

  96. Adinolfi E, Giuliani AL, De Marchi E, Pegoraro A, Orioli E, Di Virgilio F (2018) The P2X7 receptor: a main player in inflammation. Biochem Pharmacol:151234–151244. https://doi.org/10.1016/j.bcp.2017.12.021

  97. Hill LM, Gavala ML, Lenertz LY, Bertics PJ (2010) Extracellular ATP may contribute to tissue repair by rapidly stimulating purinergic receptor X7-dependent vascular endothelial growth factor release from primary human monocytes. J Immunol 185(5):3028–3034. https://doi.org/10.4049/jimmunol.1001298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Liu Y, Xiao Y, Li Z (2011) P2X7 receptor positively regulates MyD88-dependent NF-kappaB activation. Cytokine 55(2):229–236. https://doi.org/10.1016/j.cyto.2011.05.003

    Article  CAS  PubMed  Google Scholar 

  99. Swanson KV, Deng M, Ting JP (2019) The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol 19(8):477–489. https://doi.org/10.1038/s41577-019-0165-0

    Article  CAS  PubMed  Google Scholar 

  100. Amores-Iniesta J, Barbera-Cremades M, Martinez CM, Pons JA, Revilla-Nuin B, Martinez-Alarcon L, Di Virgilio F, Parrilla P, Baroja-Mazo A, Pelegrin P (2017) Extracellular ATP activates the NLRP3 Inflammasome and is an early danger signal of skin allograft rejection. Cell Rep 21(12):3414–3426. https://doi.org/10.1016/j.celrep.2017.11.079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Ratajczak MZ, Mack A, Bujko K, Domingues A, Pedziwiatr D, Kucia M, Ratajczak J, Ulrich H, Kucharska-Mazur J, Samochowiec J (2019) ATP-Nlrp3 inflammasome-complement cascade axis in sterile brain inflammation in psychiatric patients and its impact on stem cell trafficking. Stem Cell Rev Rep 15(4):497–505. https://doi.org/10.1007/s12015-019-09888-1

    Article  PubMed  Google Scholar 

  102. Adamiak M, Bujko K, Cymer M, Plonka M, Glaser T, Kucia M, Ratajczak J, Ulrich H, Abdel-Latif A, Ratajczak MZ (2018) Novel evidence that extracellular nucleotides and purinergic signaling induce innate immunity-mediated mobilization of hematopoietic stem/progenitor cells. Leukemia 32(9):1920–1931. https://doi.org/10.1038/s41375-018-0122-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Lenkiewicz AM, Adamiak M, Thapa A, Bujko K, Pedziwiatr D, Abdel-Latif AK, Kucia M, Ratajczak J, Ratajczak MZ (2019) The Nlrp3 inflammasome orchestrates mobilization of bone marrow-residing stem cells into peripheral blood. Stem Cell Rev Rep 15(3):391–403. https://doi.org/10.1007/s12015-019-09890-7

    Article  CAS  PubMed  Google Scholar 

  104. Adamiak M, Bujko K, Brzezniakiewicz-Janus K, Kucia M, Ratajczak J, Ratajczak MZ (2019) The inhibition of CD39 and CD73 cell surface ectonucleotidases by small molecular inhibitors enhances the mobilization of bone marrow residing stem cells by decreasing the extracellular level of adenosine. Stem Cell Rev Rep. https://doi.org/10.1007/s12015-019-09918-y

  105. Borges da Silva H, Beura LK, Wang H, Hanse EA, Gore R, Scott MC, Walsh DA, Block KE, Fonseca R, Yan Y, Hippen KL, Blazar BR, Masopust D, Kelekar A, Vulchanova L, Hogquist KA, Jameson SC (2018) The purinergic receptor P2RX7 directs metabolic fitness of long-lived memory CD8(+) T cells. Nature 559(7713):264–268. https://doi.org/10.1038/s41586-018-0282-0

    Article  CAS  PubMed  Google Scholar 

  106. Burnstock G, Knight GE (2018) The potential of P2X7 receptors as a therapeutic target, including inflammation and tumour progression. Purinergic Signal 14(1):1–18. https://doi.org/10.1007/s11302-017-9593-0

    Article  CAS  PubMed  Google Scholar 

  107. Graziano F, Desdouits M, Garzetti L, Podini P, Alfano M, Rubartelli A, Furlan R, Benaroch P, Poli G (2015) Extracellular ATP induces the rapid release of HIV-1 from virus containing compartments of human macrophages. Proc Natl Acad Sci U S A 112(25):E3265–E3273. https://doi.org/10.1073/pnas.1500656112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Lee R, Williams JC, Mackman N (2012) P2X7 regulation of macrophage tissue factor activity and microparticle generation. J Thromb Haemost 10(9):1965–1967. https://doi.org/10.1111/j.1538-7836.2012.04842.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Di Virgilio F, Dal Ben D, Sarti AC, Giuliani AL, Falzoni S (2017) The P2X7 receptor in infection and inflammation. Immunity 47(1):15–31. https://doi.org/10.1016/j.immuni.2017.06.020

    Article  CAS  PubMed  Google Scholar 

  110. Solini A, Chiozzi P, Morelli A, Fellin R, Di Virgilio F (1999) Human primary fibroblasts in vitro express a purinergic P2X7 receptor coupled to ion fluxes, microvesicle formation and IL-6 release. J Cell Sci 112(Pt 3):297–305

    CAS  PubMed  Google Scholar 

  111. Kurashima Y, Amiya T, Nochi T, Fujisawa K, Haraguchi T, Iba H, Tsutsui H, Sato S, Nakajima S, Iijima H, Kubo M, Kunisawa J, Kiyono H (2012) Extracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors. Nat Commun 31034. https://doi.org/10.1038/ncomms2023

  112. Bianchi G, Vuerich M, Pellegatti P, Marimpietri D, Emionite L, Marigo I, Bronte V, Di Virgilio F, Pistoia V, Raffaghello L (2014) ATP/P2X7 axis modulates myeloid-derived suppressor cell functions in neuroblastoma microenvironment. Cell Death Dis:5e1135. https://doi.org/10.1038/cddis.2014.109

  113. Nogueira-Pedro A, Dias CC, Regina H, Segreto C, Addios PC, Lungato L, D’Almeida V, Barros CC, Higa EM, Buri MV, Ferreira AT, Paredes-Gamero EJ (2014) Nitric oxide-induced murine hematopoietic stem cell fate involves multiple signaling proteins, gene expression, and redox modulation. Stem Cells 32(11):2949–2960. https://doi.org/10.1002/stem.1773

    Article  CAS  PubMed  Google Scholar 

  114. Paredes-Gamero EJ, Barbosa CM, Ferreira AT (2012) Calcium signaling as a regulator of hematopoiesis. Front Biosci (Elite Ed), 41375-84.

  115. Lemoli RM, Ferrari D, Fogli M, Rossi L, Pizzirani C, Forchap S, Chiozzi P, Vaselli D, Bertolini F, Foutz T, Aluigi M, Baccarani M, Di Virgilio F (2004) Extracellular nucleotides are potent stimulators of human hematopoietic stem cells in vitro and in vivo. Blood 104(6):1662–1670. https://doi.org/10.1182/blood-2004-03-0834

    Article  CAS  PubMed  Google Scholar 

  116. 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 516. https://doi.org/10.1186/1471-2172-5-16

  117. Rossi L, Manfredini R, Bertolini F, Ferrari D, Fogli M, Zini R, Salati S, Salvestrini V, Gulinelli S, Adinolfi E, Ferrari S, Di Virgilio F, Baccarani M, Lemoli RM (2007) The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration. Blood 109(2):533–542. https://doi.org/10.1182/blood-2006-01-035634

    Article  CAS  PubMed  Google Scholar 

  118. Paredes-Gamero EJ, Leon CM, Borojevic R, Oshiro ME, Ferreira AT (2008) Changes in intracellular Ca2+ levels induced by cytokines and P2 agonists differentially modulate proliferation or commitment with macrophage differentiation in murine hematopoietic cells. J Biol Chem 283(46):31909–31919. https://doi.org/10.1074/jbc.M801990200

    Article  CAS  PubMed  Google Scholar 

  119. Barbosa CM, Leon CM, Nogueira-Pedro A, Wasinsk F, Araujo RC, Miranda A, Ferreira AT, Paredes-Gamero EJ (2011) Differentiation of hematopoietic stem cell and myeloid populations by ATP is modulated by cytokines. Cell Death Dis:2e165. https://doi.org/10.1038/cddis.2011.49

  120. Cho J, Yusuf R, Kook S, Attar E, Lee D, Park B, Cheng T, Scadden DT, Lee BC (2014) Purinergic P2Y(1)(4) receptor modulates stress-induced hematopoietic stem/progenitor cell senescence. J Clin Invest 124(7):3159–3171. https://doi.org/10.1172/JCI61636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Feng W, Yang F, Wang R, Yang X, Wang L, Chen C, Liao J, Lin Y, Ren Q, Zheng G (2016) High level P2X7-mediated signaling impairs function of hematopoietic stem/progenitor cells. Stem Cell Rev 12(3):305–314. https://doi.org/10.1007/s12015-016-9651-y

    Article  CAS  Google Scholar 

  122. Koldej R, Collins J, Ritchie D (2018) P2X7 polymorphisms and stem cell mobilisation. Leukemia 32(12):2724–2726. https://doi.org/10.1038/s41375-018-0232-8

    Article  PubMed  Google Scholar 

  123. Hirata Y, Furuhashi K, Ishii H, Li HW, Pinho S, Ding L, Robson SC, Frenette PS, Fujisaki J (2018) CD150(high) Bone marrow tregs maintain hematopoietic stem cell quiescence and immune privilege via adenosine. Cell Stem Cell 22(3):445–453 e5. https://doi.org/10.1016/j.stem.2018.01.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Hirata Y, Kakiuchi M, Robson SC, Fujisaki J (2018) CD150high CD4 T cells and CD150high Tregs regulate hematopoietic stem cell quiescence via CD73. Haematologica. https://doi.org/10.3324/haematol.2018.198283

  125. Montero M, Garcia-Sancho J, Alvarez J (1995) Biphasic and differential modulation of Ca2+ entry by ATP and UTP in promyelocytic leukaemia HL60 cells. Biochemical Journal 305(3):879–887

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Biffen M, Alexander DR (1994) Mobilization of intracellular Ca2+ by adenine nucleotides in human T-leukaemia cells: evidence for ADP-specific and P2y-purinergic receptors. Biochemical Journal 304(3):769–774

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Communi D, Janssens R, Robaye B, Zeelis N, Boeynaems J-M (2000) Rapid up-regulation of P2Y messengers during granulocytic differentiation of HL-60 cells. FEBS Lett 475(1):39–42

    CAS  PubMed  Google Scholar 

  128. Adrian K, Bernhard MK, Breitinger HG, Ogilvie A (2000) Expression of purinergic receptors (ionotropic P2X1-7 and metabotropic P2Y1-11) during myeloid differentiation of HL60 cells. Biochim Biophys Acta 1492(1):127–138

    CAS  PubMed  Google Scholar 

  129. Zoetewij JP, van de Water B, de Bont HJ, Nagelkerke JF (1996) The role of a purinergic P2z receptor in calcium-dependent cell killing of isolated rat hepatocytes by extracellular adenosine triphosphate. Hepatology 23(4):858–865. https://doi.org/10.1002/hep.510230429

    Article  CAS  PubMed  Google Scholar 

  130. Yu T, Junger WG, Yuan C, Jin A, Zhao Y, Zheng X, Zeng Y, Liu J (2010) Shockwaves increase T-cell proliferation and IL-2 expression through ATP release, P2X7 receptors, and FAK activation. Am J Physiol Cell Physiol 298(3):C457–C464. https://doi.org/10.1152/ajpcell.00342.2009

    Article  CAS  PubMed  Google Scholar 

  131. Zhang X-J, Zheng G-G, Ma X-T, Yang Y-H, Li G, Rao Q, Nie K, Wu K-F (2004) Expression of P2X7 in human hematopoietic cell lines and leukemia patients. Leuk Res 28(12):1313–1322. https://doi.org/10.1016/j.leukres.2004.04.001

    Article  CAS  PubMed  Google Scholar 

  132. Gadeock S, Pupovac A, Sluyter V, Spildrejorde M, Sluyter R (2012) P2X7 receptor activation mediates organic cation uptake into human myeloid leukaemic KG-1 cells. Purinergic Signal 8(4):669–676

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Constantinescu P, Wang B, Kovacevic K, Jalilian I, Bosman GJ, Wiley JS, Sluyter R (2010) P2X7 receptor activation induces cell death and microparticle release in murine erythroleukemia cells. Biochimica et Biophysica Acta (BBA)-Biomembranes 1798(9):1797–1804

    CAS  Google Scholar 

  134. Chong JH, Zheng GG, Zhu XF, Guo Y, Wang L, Ma CH, Liu SY, Xu LL, Lin YM, Wu KF (2010) Abnormal expression of P2X family receptors in Chinese pediatric acute leukemias. Biochem Biophys Res Commun 391(1):498–504. https://doi.org/10.1016/j.bbrc.2009.11.087

    Article  CAS  PubMed  Google Scholar 

  135. Salvestrini V, Orecchioni S, Talarico G, Reggiani F, Mazzetti C, Bertolini F, Orioli E, Adinolfi E, Di Virgilio F, Pezzi A, Cavo M, Lemoli RM, Curti A (2017) Extracellular ATP induces apoptosis through P2X7R activation in acute myeloid leukemia cells but not in normal hematopoietic stem cells. Oncotarget 8(4):5895–5908. https://doi.org/10.18632/oncotarget.13927

    Article  PubMed  Google Scholar 

  136. Salvestrini V, Zini R, Rossi L, Gulinelli S, Manfredini R, Bianchi E, Piacibello W, Caione L, Migliardi G, Ricciardi MR (2012) Purinergic signaling inhibits human acute myeloblastic leukemia cell proliferation, migration, and engraftment in immunodeficient mice. Blood 119(1):217–226

    CAS  PubMed  Google Scholar 

  137. Lecciso M, Ocadlikova D, Sangaletti S, Trabanelli S, De Marchi E, Orioli E, Pegoraro A, Portararo P, Jandus C, Bontadini A, Redavid A, Salvestrini V, Romero P, Colombo MP, Di Virgilio F, Cavo M, Adinolfi E, Curti A (2017) ATP release from chemotherapy-treated dying leukemia cells elicits an immune suppressive effect by increasing regulatory T cells and tolerogenic dendritic cells. Front Immunol:81918. https://doi.org/10.3389/fimmu.2017.01918

  138. Wang W, Xiao J, Adachi M, Liu Z, Zhou J (2011) 4-aminopyridine induces apoptosis of human acute myeloid leukemia cells via increasing [Ca2+]i through P2X7 receptor pathway. Cell Physiol Biochem 28(2):199–208. https://doi.org/10.1159/000331731

    Article  CAS  PubMed  Google Scholar 

  139. Yoon MJ, Lee HJ, Kim JH, Kim DK (2006) Extracellular ATP induces apoptotic signaling in human monocyte leukemic cells, HL-60 and F-36P. Arch Pharm Res 29(11):1032–1041

    CAS  PubMed  Google Scholar 

  140. Zhang X, Meng L, He B, Chen J, Liu P, Zhao J, Zhang Y, Li M, An D (2009) The role of P2X7 receptor in ATP-mediated human leukemia cell death: calcium influx-independent. Acta Biochim Biophys Sin (Shanghai) 41(5):362–369

    Google Scholar 

  141. Wang B, Sluyter R (2013) P2X7 receptor activation induces reactive oxygen species formation in erythroid cells. Purinergic Signal 9(1):101–112. https://doi.org/10.1007/s11302-012-9335-2

    Article  CAS  PubMed  Google Scholar 

  142. Ledderose C, Woehrle T, Ledderose S, Strasser K, Seist R, Bao Y, Zhang J, Junger WG (2016) Cutting off the power: inhibition of leukemia cell growth by pausing basal ATP release and P2X receptor signaling? Purinergic Signal 12(3):439–451. https://doi.org/10.1007/s11302-016-9510-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK (1999) Unmutated Ig VH genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 94(6):1848–1854

    CAS  Google Scholar 

  144. Di Virgilio F, Wiley JS (2002) The P2X7 receptor of CLL lymphocytes-a molecule with a split personality. The Lancet 360(9349):1898–1899

    Google Scholar 

  145. Adinolfi E, Melchiorri L, Falzoni S, Chiozzi P, Morelli A, Tieghi A, Cuneo A, Castoldi G, Di Virgilio F, Baricordi OR (2002) P2X7 receptor expression in evolutive and indolent forms of chronic B lymphocytic leukemia. Blood 99(2):706–708

    CAS  PubMed  Google Scholar 

  146. Thunberg U, Tobin G, Johnson A, Söderberg O, Padyukov L, Hultdin M, Klareskog L, Enblad G, Sundström C, Roos G (2002) Polymorphism in the P2X7 receptor gene and survival in chronic lymphocytic leukaemia. The Lancet 360(9349):1935–1939

    CAS  Google Scholar 

  147. Nückel H, Frey UH, Dürig J, Dührsen U, Siffert W (2004) 1513A/C polymorphism in the P2X7 receptor gene in chronic lymphocytic leukemia: absence of correlation with clinical outcome. Eur J Haematol 72(4):259–263

    PubMed  Google Scholar 

  148. Sellick GS, Rudd M, Eve P, Allinson R, Matutes E, Catovsky D, Houlston RS (2004) The P2X7 receptor gene A1513C polymorphism does not contribute to risk of familial or sporadic chronic lymphocytic leukemia. Cancer Epidemiol Prev Biomarkers 13(6):1065–1067

    CAS  Google Scholar 

  149. Starczynski J, Pepper C, Pratt G, Hooper L, Thomas A, Hoy T, Milligan D, Bentley P, Fegan C (2003) The P2X7 receptor gene polymorphism 1513 A → C has no effect on clinical prognostic markers, in vitro sensitivity to fludarabine, Bcl-2 family protein expression or survival in B-cell chronic lymphocytic leukaemia. Br J Haematol 123(1):66–71

    CAS  PubMed  Google Scholar 

  150. Zhang L, Ibbotson R, Orchard J, Gardiner A, Seear R, Chase A, Oscier D, Cross N (2003) P2X7 polymorphism and chronic lymphocytic leukaemia: lack of correlation with incidence, survival and abnormalities of chromosome 12. Leukemia 17(11):2097

    CAS  PubMed  Google Scholar 

  151. Salaro E, Rambaldi A, Falzoni S, Amoroso FS, Franceschini A, Sarti AC, Bonora M, Cavazzini F, Rigolin GM, Ciccone M, Audrito V, Deaglio S, Pelegrin P, Pinton P, Cuneo A, Di Virgilio F (2016) Involvement of the P2X7-NLRP3 axis in leukemic cell proliferation and death. Sci Rep 626280. https://doi.org/10.1038/srep26280

  152. Zychlinsky A, Prevost MC, Sansonetti PJ (1992) Shigella flexneri induces apoptosis in infected macrophages. Nature 358(6382):167–169. https://doi.org/10.1038/358167a0

    Article  CAS  PubMed  Google Scholar 

  153. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW, Annicchiarico-Petruzzelli M, Antonov AV, Arama E, Baehrecke EH, Barlev NA, Bazan NG, Bernassola F, Bertrand MJM, Bianchi K, Blagosklonny MV, Blomgren K, Borner C, Boya P, Brenner C, Campanella M, Candi E, Carmona-Gutierrez D, Cecconi F, Chan FK, Chandel NS, Cheng EH, Chipuk JE, Cidlowski JA, Ciechanover A, Cohen GM, Conrad M, Cubillos-Ruiz JR, Czabotar PE, D’Angiolella V, Dawson TM, Dawson VL, De Laurenzi V, De Maria R, Debatin KM, DeBerardinis RJ, Deshmukh M, Di Daniele N, Di Virgilio F, Dixit VM, Dixon SJ, Duckett CS, Dynlacht BD, El-Deiry WS, Elrod JW, Fimia GM, Fulda S, Garcia-Saez AJ, Garg AD, Garrido C, Gavathiotis E, Golstein P, Gottlieb E, Green DR, Greene LA, Gronemeyer H, Gross A, Hajnoczky G, Hardwick JM, Harris IS, Hengartner MO, Hetz C, Ichijo H, Jaattela M, Joseph B, Jost PJ, Juin PP, Kaiser WJ, Karin M, Kaufmann T, Kepp O, Kimchi A, Kitsis RN, Klionsky DJ, Knight RA, Kumar S, Lee SW, Lemasters JJ, Levine B, Linkermann A, Lipton SA, Lockshin RA, Lopez-Otin C, Lowe SW, Luedde T, Lugli E, MacFarlane M, Madeo F, Malewicz M, Malorni W, Manic G, Marine JC, Martin SJ, Martinou JC, Medema JP, Mehlen P, Meier P, Melino S, Miao EA, Molkentin JD, Moll UM, Munoz-Pinedo C, Nagata S, Nunez G, Oberst A, Oren M, Overholtzer M, Pagano M, Panaretakis T, Pasparakis M, Penninger JM, Pereira DM, Pervaiz S, Peter ME, Piacentini M, Pinton P, Prehn JHM, Puthalakath H, Rabinovich GA, Rehm M, Rizzuto R, Rodrigues CMP, Rubinsztein DC, Rudel T, Ryan KM, Sayan E, Scorrano L, Shao F, Shi Y, Silke J, Simon HU, Sistigu A, Stockwell BR, Strasser A, Szabadkai G, Tait SWG, Tang D, Tavernarakis N, Thorburn A, Tsujimoto Y, Turk B, Vanden Berghe T, Vandenabeele P, Vander Heiden MG, Villunger A, Virgin HW, Vousden KH, Vucic D, Wagner EF, Walczak H, Wallach D, Wang Y, Wells JA, Wood W, Yuan J, Zakeri Z, Zhivotovsky B, Zitvogel L, Melino G, Kroemer G (2018) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 25(3):486–541. https://doi.org/10.1038/s41418-017-0012-4

    Article  PubMed  PubMed Central  Google Scholar 

  154. Wang D, Zheng J, Hu Q, Zhao C, Chen Q, Shi P, Chen Q, Zou Y, Zou D, Liu Q, Pei J, Wu X, Gao X, Ren J, Lin Z (2019) Magnesium protects against sepsis by blocking gasdermin D N-terminal-induced pyroptosis. Cell Death Differ. https://doi.org/10.1038/s41418-019-0366-x

  155. Yang D, He Y, Munoz-Planillo R, Liu Q, Nunez G (2015) Caspase-11 requires the pannexin-1 channel and the purinergic P2X7 pore to mediate pyroptosis and endotoxic shock. Immunity 43(5):923–932. https://doi.org/10.1016/j.immuni.2015.10.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Faliti CE, Gualtierotti R, Rottoli E, Gerosa M, Perruzza L, Romagnani A, Pellegrini G, De Ponte CB, Rossi RL, Idzko M, Mazza EMC, Bicciato S, Traggiai E, Meroni PL, Grassi F (2019) P2X7 receptor restrains pathogenic Tfh cell generation in systemic lupus erythematosus. J Exp Med 216(2):317–336. https://doi.org/10.1084/jem.20171976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Mitra S, Sarkar A (2019) Microparticulate P2X7 and GSDM-D mediated regulation of functional IL-1beta release. Purinergic Signal 15(1):119–123. https://doi.org/10.1007/s11302-018-9640-5

    Article  CAS  PubMed  Google Scholar 

  158. Clifford EE, Parker K, Humphreys BD, Kertesy SB, Dubyak GR (1998) The P2X1 receptor, an adenosine triphosphate-gated cation channel, is expressed in human platelets but not in human blood leukocytes. Blood 91(9):3172–3181

    CAS  PubMed  Google Scholar 

  159. Gachet C (2001) Identification, characterization, and inhibition of the platelet ADP receptors. Int J Hematol 74(4):375–381

    CAS  PubMed  Google Scholar 

  160. Hall DA, Hourani SM (1994) Effects of suramin on increases in cytosolic calcium and on inhibition of adenylate cyclase induced by adenosine 5′-diphosphate in human platelets. Biochem Pharmacol 47(6):1013–1018

    CAS  PubMed  Google Scholar 

  161. Hechler B, Vigne P, Leon C, Breittmayer JP, Gachet C, Frelin C (1998) ATP derivatives are antagonists of the P2Y1 receptor: similarities to the platelet ADP receptor. Mol Pharmacol 53(4):727–733

    CAS  PubMed  Google Scholar 

  162. Fagura MS, Dainty IA, McKay GD, Kirk IP, Humphries RG, Robertson MJ, Dougall IG, Leff P (1998) P2Y1-receptors in human platelets which are pharmacologically distinct from P2Y(ADP)-receptors. Br J Pharmacol 124(1):157–164. https://doi.org/10.1038/sj.bjp.0701827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Waldo GL, Corbitt J, Boyer JL, Ravi G, Kim HS, Ji XD, Lacy J, Jacobson KA, Harden TK (2002) Quantitation of the P2Y(1) receptor with a high affinity radiolabeled antagonist. Mol Pharmacol 62(5):1249–1257. https://doi.org/10.1124/mol.62.5.1249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Burnstock G, Knight GE (2004) Cellular distribution and functions of P2 receptor subtypes in different systems. Int Rev Cytol:24031–24304. https://doi.org/10.1016/S0074-7696(04)40002-3

  165. Maffrand JP, Bernat A, Delebassée D, Defreyn G, Cazenave JP, Gordon JL (1988) ADP plays a key role in thrombogenesis in rats. Thromb Haemost 59(2):225–230

    CAS  PubMed  Google Scholar 

  166. Savi P, Pereillo JM, Uzabiaga MF, Combalbert J, Picard C, Maffrand JP, Pascal M, Herbert JM (2000) Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost 84(5):891–896

    CAS  PubMed  Google Scholar 

  167. Boeynaems JM, van Giezen H, Savi P, Herbert JM (2005) P2Y receptor antagonists in thrombosis. Curr Opin Investig Drugs 6(3):275–282

    CAS  PubMed  Google Scholar 

  168. Kunapuli SP, Ding Z, Dorsam RT, Kim S, Murugappan S, Quinton TM (2003) ADP receptors--targets for developing antithrombotic agents. Curr Pharm Des 9(28):2303–2316

    CAS  PubMed  Google Scholar 

  169. Gachet C (2001) ADP receptors of platelets and their inhibition. Thromb Haemost 86(1):222–232

    CAS  PubMed  Google Scholar 

  170. Bertrand ME, Rupprecht HJ, Urban P, Gershlick AH, Investigators C (2000) Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting : the clopidogrel aspirin stent international cooperative study (CLASSICS). Circulation 102(6):624–629

    CAS  PubMed  Google Scholar 

  171. Franchi F, Angiolillo DJ (2015) Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol 12(1):30–47. https://doi.org/10.1038/nrcardio.2014.156

    Article  CAS  PubMed  Google Scholar 

  172. Sugidachi A, Ogawa T, Kurihara A, Hagihara K, Jakubowski JA, Hashimoto M, Niitsu Y, Asai F (2007) The greater in vivo antiplatelet effects of prasugrel as compared to clopidogrel reflect more efficient generation of its active metabolite with similar antiplatelet activity to that of clopidogrel’s active metabolite. J Thromb Haemost 5(7):1545–1551. https://doi.org/10.1111/j.1538-7836.2007.02598.x

    Article  CAS  PubMed  Google Scholar 

  173. Anderson SD, Shah NK, Yim J, Epstein BJ (2010) Efficacy and safety of ticagrelor: a reversible P2Y12 receptor antagonist. Ann Pharmacother 44(3):524–537. https://doi.org/10.1345/aph.1M548

    Article  CAS  PubMed  Google Scholar 

  174. Husted S, Boersma E (2016) Case study: ticagrelor in PLATO and Prasugrel in TRITON-TIMI 38 and TRILOGY-ACS trials in patients with acute coronary syndromes. Am J Ther 23(6):e1876–e1889. https://doi.org/10.1097/MJT.0000000000000237

    Article  PubMed  Google Scholar 

  175. Patelis N, Kakavia K, Maltezos K, Damascos C, Spartalis E, Matheiken S, Georgopoulos S (2018) An update on novel antiplatelets in vascular patients. Curr Pharm Des. https://doi.org/10.2174/1381612825666181226144129

  176. Xiang B, Zhang G, Ren H, Sunkara M, Morris AJ, Gartner TK, Smyth SS, Li Z (2012) The P2Y(12) antagonists, 2MeSAMP and cangrelor, inhibit platelet activation through P2Y(12)/G(i)-dependent mechanism. PLoS One 7(12):e51037. https://doi.org/10.1371/journal.pone.0051037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Franchi F, Rollini F, Muñiz-Lozano A, Cho JR, Angiolillo DJ (2013) Cangrelor: a review on pharmacology and clinical trial development. Expert Rev Cardiovasc Ther 11(10):1279–1291. https://doi.org/10.1586/14779072.2013.837701

    Article  CAS  PubMed  Google Scholar 

  178. Welsh RC, Rao SV, Zeymer U, Thompson VP, Huber K, Kochman J, McClure MW, Gretler DD, Bhatt DL, Gibson CM, Angiolillo DJ, Gurbel PA, Berdan LG, Paynter G, Leonardi S, Madan M, French WJ, Harrington RA, Investigators I-P (2012) A randomized, double-blind, active-controlled phase 2 trial to evaluate a novel selective and reversible intravenous and oral P2Y12 inhibitor elinogrel versus clopidogrel in patients undergoing nonurgent percutaneous coronary intervention: the INNOVATE-PCI trial. Circ Cardiovasc Interv 5(3):336–346. https://doi.org/10.1161/CIRCINTERVENTIONS.111.964197

    Article  CAS  PubMed  Google Scholar 

  179. Pfefferkorn JA, Choi C, Winters T, Kennedy R, Chi L, Perrin LA, Lu G, Ping YW, McClanahan T, Schroeder R, Leininger MT, Geyer A, Schefzick S, Atherton J (2008) P2Y1 receptor antagonists as novel antithrombotic agents. Bioorg Med Chem Lett 18(11):3338–3343. https://doi.org/10.1016/j.bmcl.2008.04.028

    Article  CAS  PubMed  Google Scholar 

  180. Hechler B, Nonne C, Roh EJ, Cattaneo M, Cazenave JP, Lanza F, Jacobson KA, Gachet C (2006) MRS2500 [2-iodo-N6-methyl-(N)-methanocarba-2′-deoxyadenosine-3′,5′-bisphosphate], a potent, selective, and stable antagonist of the platelet P2Y1 receptor with strong antithrombotic activity in mice. J Pharmacol Exp Ther 316(2):556–563. https://doi.org/10.1124/jpet.105.094037

    Article  CAS  PubMed  Google Scholar 

  181. Dunn PM, Blakeley AG (1988) Suramin: a reversible P2-purinoceptor antagonist in the mouse vas deferens. Br J Pharmacol 93(2):243–245

    CAS  PubMed  PubMed Central  Google Scholar 

  182. Lambrecht G, Braun K, Damer M, Ganso M, Hildebrandt C, Ullmann H, Kassack MU, Nickel P (2002) Structure-activity relationships of suramin and pyridoxal-5′-phosphate derivatives as P2 receptor antagonists. Curr Pharm Des 8(26):2371–2399

    CAS  PubMed  Google Scholar 

  183. Murakami T, Fujihara T, Horibe Y, Nakamura M (2004) Diquafosol elicits increases in net Cl- transport through P2Y2 receptor stimulation in rabbit conjunctiva. Ophthalmic Res 36(2):89–93. https://doi.org/10.1159/000076887

    Article  CAS  PubMed  Google Scholar 

  184. Fujihara T, Murakami T, Nagano T, Nakamura M, Nakata K (2002) INS365 suppresses loss of corneal epithelial integrity by secretion of mucin-like glycoprotein in a rabbit short-term dry eye model. J Ocul Pharmacol Ther 18(4):363–370. https://doi.org/10.1089/10807680260218524

    Article  CAS  PubMed  Google Scholar 

  185. Buisseret L, Pommey S, Allard B, Garaud S, Bergeron M, Cousineau I, Ameye L, Bareche Y, Paesmans M, Crown JPA, Di Leo A, Loi S, Piccart-Gebhart M, Willard-Gallo K, Sotiriou C, Stagg J (2018) Clinical significance of CD73 in triple-negative breast cancer: multiplex analysis of a phase III clinical trial. Ann Oncol 29(4):1056–1062. https://doi.org/10.1093/annonc/mdx730

    Article  CAS  PubMed  Google Scholar 

  186. Allard D, Chrobak P, Allard B, Messaoudi N, Stagg J (2018) Targeting the CD73-adenosine axis in immuno-oncology. Immunol Lett. https://doi.org/10.1016/j.imlet.2018.05.001

Download references

Funding

This publication and the previous related results were supported by “Fundação de Amparo à Pesquisa do Estado de São Paulo” (FAPESP. Proc. 2018/23870-4) and “Conselho Nacional de Desenvolvimento Científico e Tecnológico” (CNPq 425965/2018-0).

Author information

Authors and Affiliations

  1. Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, 79070-900, Brazil

    Kelly Juliana Filippin, Dhébora Albuquerque Dias, Eduardo Benedetti Parisotto & Edgar J. Paredes-Gamero

  2. Departamento de Bioquímica, Universidade Federal de São Paulo, R. Três de Maio 100, São Paulo, SP, 04044-020, Brazil

    Kamylla F. S. de Souza, Roberto Theodoro de Araujo Júnior, Heron Fernandes Vieira Torquato & Edgar J. Paredes-Gamero

  3. Universidade Braz Cubas, Av. Francisco Rodrigues Filho 1233, Mogi das Cruzes, SP, 08773-380, Brazil

    Heron Fernandes Vieira Torquato

  4. Departamento de Biofísica, Universidade Federal de São Paulo, R. Botucatu 862, São Paulo, SP, 04023-062, Brazil

    Alice Teixeira Ferreira

  5. Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição (FACFAN), Laboratório de Biologia Molecular e Culturas Celulares, Av. Costa e Silva, s/n Bairro Universitário, Campo Grande, MS, CEP: 79070-900, Brazil

    Alice Teixeira Ferreira & Edgar J. Paredes-Gamero

Authors
  1. Kelly Juliana Filippin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kamylla F. S. de Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roberto Theodoro de Araujo Júnior
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Heron Fernandes Vieira Torquato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dhébora Albuquerque Dias
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eduardo Benedetti Parisotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alice Teixeira Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Edgar J. Paredes-Gamero
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Alice Teixeira Ferreira or Edgar J. Paredes-Gamero.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Filippin, K.J., de Souza, K.F.S., de Araujo Júnior, R.T. et al. Involvement of P2 receptors in hematopoiesis and hematopoietic disorders, and as pharmacological targets. Purinergic Signalling 16, 1–15 (2020). https://doi.org/10.1007/s11302-019-09684-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11302-019-09684-z

Keywords

Search

Navigation