Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury

Purinergic Signalling

Volumn 13, Issue 3, 2017, Pages 363-386

  Hasan, Djo ^a   Blankman, Paul ^a   Nieman, Gary F ^b  

^a ERASMUS MEDICAL CENTER   (Netherlands)

^b State University of New York Upstate Medical University: College of Medicine   (United States)

Author keywords

CD39; CD73; Diffuse alveolar damage; Extracellular ATP; Purinergic signalling; Ventilation induced lung injury

Indexed keywords

5' NUCLEOTIDASE; ADENOSINE; ADENOSINE TRIPHOSPHATE; ALPHA SMOOTH MUSCLE ACTIN; BETA INTERFERON; CD39 ANTIGEN; LUNG SURFACTANT; PLASMA PROTEIN; PURINERGIC P2X1 RECEPTOR; PURINERGIC P2X3 RECEPTOR; PURINERGIC P2X4 RECEPTOR; PURINERGIC P2X7 RECEPTOR; PURINERGIC P2Y1 RECEPTOR; PURINERGIC P2Y11 RECEPTOR; PURINERGIC P2Y12 RECEPTOR; PURINERGIC P2Y13 RECEPTOR; PURINERGIC P2Y2 RECEPTOR; PURINERGIC P2Y4 RECEPTOR; PURINERGIC P2Y6 RECEPTOR; PURINERGIC RECEPTOR; SURFACTANT PROTEIN A; SURFACTANT PROTEIN B; SURFACTANT PROTEIN C; SURFACTANT PROTEIN D; TRANSFORMING GROWTH FACTOR BETA; URIDINE TRIPHOSPHATE; PURINERGIC RECEPTOR AFFECTING AGENT;

ADAPTIVE IMMUNITY; ALVEOLAR MECHANICS; ARTIFICIAL VENTILATION; CAPILLARY LEAK SYNDROME; HUMAN; IMMUNE DEFICIENCY; INFLAMMATION; INNATE IMMUNITY; LUNG ALVEOLUS EPITHELIUM CELL; LUNG ALVEOLUS SURFACE TENSION; LUNG EDEMA; LUNG FIBROSIS; LUNG INFECTION; LUNG PARENCHYMA; MECHANICAL VENTILATOR; METABOLISM; NONHUMAN; PEAK EXPIRATORY FLOW; POSITIVE END EXPIRATORY PRESSURE; PROTEIN EXPRESSION; RESPIRATORY DISTRESS SYNDROME; RESPIRATORY TRACT PARAMETERS; REVIEW; SIGNAL TRANSDUCTION; TOTAL LUNG CAPACITY; VENTILATOR INDUCED LUNG INJURY; ANIMAL; IMMUNOLOGY; LUNG INJURY; PATHOLOGY;

ADENOSINE; ANIMALS; HUMANS; IMMUNITY, INNATE; INFLAMMATION; LUNG INJURY; PURINERGIC AGENTS; RECEPTORS, PURINERGIC;

EID: 85019658541     PISSN: 15739538     EISSN: 15739546     Source Type: Journal    
DOI: 10.1007/s11302-017-9564-5     Document Type: Review

References (240)

1. Sweeney RM, McAuley DF (2016) Acute respiratory distress syndrome. Lancet (London, England). doi:10.1016/s0140-6736(16)00578-x
2. Zhang Y, Sun H, Fan L, Ma Y, Sun Y, Pu J, Yang J, Qiao J, Ma G, Liu J (2012) Acute respiratory distress syndrome induced by a swine 2009 H1N1 variant in mice. PLoS One 7(1):e29347. doi:10.1371/journal.pone.0029347
3. Xu T, Qiao J, Zhao L, Wang G, He G, Li K, Tian Y, Gao M, Wang J, Wang H, Dong C (2006) Acute respiratory distress syndrome induced by avian influenza A (H5N1) virus in mice. Am J Respir Crit Care Med 174(9):1011–1017. doi:10.1164/rccm.200511-1751OC
4. Li Y, Shan Y, Chi Y, Wen T, Han X (2014) Acute lung injury induced by H9N2 virus in mice. Chin Med J 127(20):3576–3580
5. Deng G, Bi J, Kong F, Li X, Xu Q, Dong J, Zhang M, Zhao L, Luan Z, Lv N, Qiao J (2010) Acute respiratory distress syndrome induced by H9N2 virus in mice. Arch Virol 155(2):187–195. doi:10.1007/s00705-009-0560-0
6. Protti A, Andreis DT, Milesi M, Iapichino GE, Monti M, Comini B, Pugni P, Melis V, Santini A, Dondossola D, Gatti S, Lombardi L, Votta E, Carlesso E, Gattinoni L (2015) Lung anatomy, energy load, and ventilator-induced lung injury. Intensive Care Med Exp 3(1):34. doi:10.1186/s40635-015-0070-1
7. Roy S, Habashi N, Sadowitz B, Andrews P, Ge L, Wang G, Roy P, Ghosh A, Kuhn M, Satalin J, Gatto LA, Lin X, Dean DA, Vodovotz Y, Nieman G (2013) Early airway pressure release ventilation prevents ARDS-a novel preventive approach to lung injury. Shock (Augusta, Ga) 39(1):28–38. doi:10.1097/SHK.0b013e31827b47bb
8. Kollisch-Singule M, Emr B, Smith B, Ruiz C, Roy S, Meng Q, Jain S, Satalin J, Snyder K, Ghosh A, Marx WH, Andrews P, Habashi N, Nieman GF, Gatto LA (2014) Airway pressure release ventilation reduces conducting airway micro-strain in lung injury. J Am Coll Surg 219(5):968–976
9. Andrews PL, Shiber JR, Jaruga-Killeen E, Roy S, Sadowitz B, O’Toole RV, Gatto LA, Nieman GF, Scalea T, Habashi NM (2013) Early application of airway pressure release ventilation may reduce mortality in high-risk trauma patients: a systematic review of observational trauma ARDS literature. J Trauma Acute Care Surg 75(4):635–641. doi:10.1097/TA.0b013e31829d3504
10. Emr B, Gatto LA, Roy S, Satalin J, Ghosh A, Snyder K, Andrews P, Habashi N, Marx W, Ge L, Wang G, Dean DA, Vodovotz Y, Nieman G (2013) Airway pressure release ventilation prevents ventilator-induced lung injury in normal lungs. JAMA Surg 148(11):1005–1012
11. Kollisch-Singule M, Emr B, Jain SV, Andrews P, Satalin J, Liu J, Porcellio E, Kenyon V, Wang G, Marx W, Gatto LA, Nieman GF, Habashi NM (2015) The effects of airway pressure release ventilation on respiratory mechanics in extrapulmonary lung injury. Intensive Care Med Exp 3(1):35. doi:10.1186/s40635-015-0071-0
12. Kollisch-Singule M, Emr B, Smith B, Roy S, Jain S, Satalin J, Snyder K, Andrews P, Habashi N, Bates J, Marx W, Nieman G, Gatto LA (2014) Mechanical breath profile of airway pressure release ventilation: the effect on alveolar recruitment and microstrain in acute lung injury. JAMA Surg 149(11):1138–1145. doi:10.1001/jamasurg.2014.1829
13. Roy SK, Emr B, Sadowitz B, Gatto LA, Ghosh A, Satalin JM, Snyder KP, Ge L, Wang G, Marx W, Dean D, Andrews P, Singh A, Scalea T, Habashi N, Nieman GF (2013) Preemptive application of airway pressure release ventilation prevents development of acute respiratory distress syndrome in a rat traumatic hemorrhagic shock model. Shock (Augusta, Ga) 40(3):210–216. doi:10.1097/SHK.0b013e31829efb06
14. Sadowitz B, Jain S, Kollisch-Singule M, Satalin J, Andrews P, Habashi N, Gatto LA, Nieman G (2016) Preemptive mechanical ventilation can block progressive acute lung injury. World J Crit Care Med 5(1):74–82. doi:10.5492/wjccm.v5.i1.74
15. Dreyfuss D, Hubmayr R (2016) What the concept of VILI has taught us about ARDS management. Intensive Care Med 42(5):811–813. doi:10.1007/s00134-016-4287-6
16. Nieman GF, Gatto LA, Habashi NM (2015) Impact of mechanical ventilation on the pathophysiology of progressive acute lung injury. J Appl Physiol (1985) 119(11):1245–1261
17. Slutsky AS, Ranieri VM (2013) Ventilator-induced lung injury. N Engl J Med 369(22):2126–2136
18. Gattinoni L, Marini JJ, Pesenti A, Quintel M, Mancebo J, Brochard L (2016) The “baby lung” became an adult. Intensive Care Med 42(5):663–673. doi:10.1007/s00134-015-4200-8
19. Kroon AA, Wang J, Huang Z, Cao L, Kuliszewski M, Post M (2010) Inflammatory response to oxygen and endotoxin in newborn rat lung ventilated with low tidal volume. Pediatr Res 68(1):63–69. doi:10.1203/00006450-201011001-00120
20. Protti A, Andreis DT, Monti M, Santini A, Sparacino CC, Langer T, Votta E, Gatti S, Lombardi L, Leopardi O, Masson S, Cressoni M, Gattinoni L (2013) Lung stress and strain during mechanical ventilation: any difference between statics and dynamics? Crit Care Med 41(4):1046–1055. doi:10.1097/CCM.0b013e31827417a6
21. Protti A, Maraffi T, Milesi M, Votta E, Santini A, Pugni P, Andreis DT, Nicosia F, Zannin E, Gatti S, Vaira V, Ferrero S, Gattinoni L (2016) Role of strain rate in the pathogenesis of ventilator-induced lung edema. Crit Care Med 44(9):e838–e845. doi:10.1097/ccm.0000000000001718
22. Steinberg J, Schiller HJ, Halter JM, Gatto LA, Dasilva M, Amato M, McCann UG, Nieman GF (2002) Tidal volume increases do not affect alveolar mechanics in normal lung but cause alveolar overdistension and exacerbate alveolar instability after surfactant deactivation. Crit Care Med 30(12):2675–2683. doi:10.1097/01.ccm.0000038087.84531.8d
23. Bachofen H, Schurch S (2001) Alveolar surface forces and lung architecture. Comp Biochem Physiol A Mol Integr Physiol 129(1):183–193
24. Habashi NM (2005) Other approaches to open-lung ventilation: airway pressure release ventilation. Crit Care Med 33(3 Suppl):S228–S240
25. Jain SV, Kollisch-Singule M, Sadowitz B, Dombert L, Satalin J, Andrews P, Gatto LA, Nieman GF, Habashi NM (2016) The 30-year evolution of airway pressure release ventilation (APRV). Intensive Care Med Exp 4(1):11. doi:10.1186/s40635-016-0085-2
26. Wyszogrodski I, Kyei-Aboagye K, Taeusch HW Jr, Avery ME (1975) Surfactant inactivation by hyperventilation: conservation by end-expiratory pressure. J Appl Physiol 38(3):461–466
27. Verbrugge SJ, Bohm SH, Gommers D, Zimmerman LJ, Lachmann B (1998) Surfactant impairment after mechanical ventilation with large alveolar surface area changes and effects of positive end-expiratory pressure. Br J Anaesth 80(3):360–364
28. Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A, The Acute Respiratory Distress Syndrome Network (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342(18):1301–1308. doi:10.1056/nejm200005043421801
29. Aeffner F, Bolon B, Davis IC (2015) Mouse models of acute respiratory distress syndrome: a review of analytical approaches, pathologic features, and common measurements. Toxicol Pathol 43(8):1074–1092. doi:10.1177/0192623315598399
30. Rocco PR, Nieman GF (2016) ARDS: what experimental models have taught us. Intensive Care Med 42(5):806–810. doi:10.1007/s00134-016-4268-9
31. Kao KC, Hu HC, Chang CH, Hung CY, Chiu LC, Li SH, Lin SW, Chuang LP, Wang CW, Li LF, Chen NH, Yang CT, Huang CC, Tsai YH (2015) Diffuse alveolar damage associated mortality in selected acute respiratory distress syndrome patients with open lung biopsy. Crit Care 19:228. doi:10.1186/s13054-015-0949-y
32. Lorente JA, Cardinal-Fernandez P, Munoz D, Frutos-Vivar F, Thille AW, Jaramillo C, Ballen-Barragan A, Rodriguez JM, Penuelas O, Ortiz G, Blanco J, Pinheiro BV, Nin N, del Carmen MM, Esteban A, Thompson TB (2015) Acute respiratory distress syndrome in patients with and without diffuse alveolar damage: an autopsy study. Intensive Care Med 41(11):1921–1930. doi:10.1007/s00134-015-4046-0
33. Thille AW, Esteban A, Fernandez-Segoviano P, Rodriguez JM, Aramburu JA, Penuelas O, Cortes-Puch I, Cardinal-Fernandez P, Lorente JA, Frutos-Vivar F (2013) Comparison of the berlin definition for acute respiratory distress syndrome with autopsy. Am J Respir Crit Care Med 187(7):761–767. doi:10.1164/rccm.201211-1981OC
34. Castro CY (2006) ARDS and diffuse alveolar damage: a pathologist’s perspective. Semin Thorac Cardiovasc Surg 18(1):13–19
35. Thille AW, Esteban A, Fernandez-Segoviano P, Rodriguez JM, Aramburu JA, Vargas-Errazuriz P, Martin-Pellicer A, Lorente JA, Frutos-Vivar F (2013) Chronology of histological lesions in acute respiratory distress syndrome with diffuse alveolar damage: a prospective cohort study of clinical autopsies. Lancet Respir Med 1(5):395–401. doi:10.1016/s2213-2600(13)70053-5
36. Calandrino FS Jr, Anderson DJ, Mintun MA, Schuster DP (1988) Pulmonary vascular permeability during the adult respiratory distress syndrome: a positron emission tomographic study. Am Rev Respir Dis 138(2):421–428
37. Volckaert T, De Langhe S (2014) Lung epithelial stem cells and their niches: Fgf10 takes center stage. Fibrogenesis Tissue Repair 7:8. doi:10.1186/1755-1536-7-8
38. Tomashefski JF Jr (2000) Pulmonary pathology of acute respiratory distress syndrome. Clin Chest Med 21(3):435–466
39. Fukuda Y, Ishizaki M, Masuda Y, Kimura G, Kawanami O, Masugi Y (1987) The role of intraalveolar fibrosis in the process of pulmonary structural remodeling in patients with diffuse alveolar damage. Am J Pathol 126(1):171–182
40. Whitsett JA, Weaver TE (2015) Alveolar development and disease. Am J Respir Cell Mol Biol 53(1):1–7
41. Chroneos ZC, Sever-Chroneos Z, Shepherd VL (2010) Pulmonary surfactant: an immunological perspective. Cellular Physiol Biochem: Int J Exp Cell Physiol, Biochem, Pharmacol 25(1):13–26. doi:10.1159/000272047
42. Whitsett JA, Alenghat T (2015) Respiratory epithelial cells orchestrate pulmonary innate immunity. Nat Immunol 16(1):27–35. doi:10.1038/ni.3045
43. Eltzschig HK, Sitkovsky MV, Robson SC (2012) Purinergic signaling during inflammation. N Engl J Med 367(24):2322–2333
44. Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87(2):659–797. doi:10.1152/physrev.00043.2006
45. Dahl G, Qiu F, Wang J (2013) The bizarre pharmacology of the ATP release channel pannexin1. Neuropharmacol 75:583–593. doi:10.1016/j.neuropharm.2013.02.019
46. Ravichandran KS (2011) Beginnings of a good apoptotic meal: the find-me and eat-me signaling pathways. Immunity 35(4):445–455. doi:10.1016/j.immuni.2011.09.004
47. Eltzschig HK, Eckle T, Mager A, Kuper N, Karcher C, Weissmuller T, Boengler K, Schulz R, Robson SC, Colgan SP (2006) ATP release from activated neutrophils occurs via connexin 43 and modulates adenosine-dependent endothelial cell function. Circ Res 99(10):1100–1108. doi:10.1161/01.res.0000250174.31269.70
48. Faigle M, Seessle J, Zug S, El Kasmi KC, Eltzschig HK (2008) ATP release from vascular endothelia occurs across Cx43 hemichannels and is attenuated during hypoxia. PLoS One 3(7):e2801. doi:10.1371/journal.pone.0002801
49. Fields RD (2011) Nonsynaptic and nonvesicular ATP release from neurons and relevance to neuron-glia signaling. Semin Cell Dev Biol 22(2):214–219. doi:10.1016/j.semcdb.2011.02.009
50. Suadicani SO, Brosnan CF, Scemes E (2006) P2X7 receptors mediate ATP release and amplification of astrocytic intercellular Ca2+ signaling. J Neurosci: Off J Soc Neurosci 26(5):1378–1385. doi:10.1523/jneurosci.3902-05.2006
51. Brandao-Burch A, Key ML, Patel JJ, Arnett TR, Orriss IR (2012) The P2X7 receptor is an important regulator of extracellular ATP levels. Front Endocrinol 3:41. doi:10.3389/fendo.2012.00041
52. Verkhratsky A, Burnstock G (2014) Biology of purinergic signalling: its ancient evolutionary roots, its omnipresence and its multiple functional significance. BioEssays 36(7):697–705
53. Idzko M, Ferrari D, Eltzschig HK (2014) Nucleotide signalling during inflammation. Nature 509(7500):310–317
54. Mishra A, Chintagari NR, Guo Y, Weng T, Su L, Liu L (2011) Purinergic P2X7 receptor regulates lung surfactant secretion in a paracrine manner. J Cell Sci 124(Pt 4):657–668
55. Dietl P, Haller T, Frick M (2012) Spatio-temporal aspects, pathways and actions of Ca(2+) in surfactant secreting pulmonary alveolar type II pneumocytes. Cell Calcium 52(3–4):296–302
56. Thompson KE, Korbmacher JP, Hecht E, Hobi N, Wittekindt OH, Dietl P, Kranz C, Frick M (2013) Fusion-activated cation entry (FACE) via P2X(4) couples surfactant secretion and alveolar fluid transport. FASEB J 27(4):1772–1783
57. Patel AS, Reigada D, Mitchell CH, Bates SR, Margulies SS, Koval M (2005) Paracrine stimulation of surfactant secretion by extracellular ATP in response to mechanical deformation. Am J Physiol Lung Cell Mol Physiol 289(3):L489–L496
58. Furuya K, Tan JJ, Boudreault F, Sokabe M, Berthiaume Y, Grygorczyk R (2016) Real-time imaging of inflation-induced ATP release in the ex-vivo rat lung. Am J Physiol Lung Cell Mol Physiol:ajplung. doi:10.1152/ajplung.00425.2015
59. Miklavc P, Mair N, Wittekindt OH, Haller T, Dietl P, Felder E, Timmler M, Frick M (2011) Fusion-activated Ca2+ entry via vesicular P2X4 receptors promotes fusion pore opening and exocytotic content release in pneumocytes. Proc Natl Acad Sci USA 108(35):14503–14508
60. Chander A, Sen N, Wu AM, Spitzer AR (1995) Protein kinase C in ATP regulation of lung surfactant secretion in type II cells. Am J Phys 268(1 Pt 1):L108–L116
61. Gutierrez AM, Lou X, Erik A, Persson G, Ring A (1999) Ca2+ response of rat mesangial cells to ATP analogues. Eur J Pharmacol 369(1):107–112
62. Gutierrez AM, Lou X, Erik A, Persson G, Ring A (2000) Growth hormones reverse desensitization of P2Y(2) receptors in rat mesangial cells. Biochem Biophys Res Commun 270(2):594–599. doi:10.1006/bbrc.2000.2461
63. Yan Z, Liang Z, Obsil T, Stojilkovic SS (2006) Participation of the Lys313-Ile333 sequence of the purinergic P2X4 receptor in agonist binding and transduction of signals to the channel gate. J Biol Chem 281(43):32649–32659. doi:10.1074/jbc.M512791200
64. North RA (2002) Molecular physiology of P2X receptors. Physiol Rev 82(4):1013–1067. doi:10.1152/physrev.00015.2002
65. Venereau E, Ceriotti C, Bianchi ME (2015) DAMPs from cell death to new life. Front Immunol 6:422. doi:10.3389/fimmu.2015.00422
66. Calkovska A, Uhliarova B, Joskova M, Franova S, Kolomaznik M, Calkovsky V, Smolarova S (2015) Pulmonary surfactant in the airway physiology: a direct relaxing effect on the smooth muscle. Respir Physiol Neurobiol 209:95–105
67. Maidji E, Kosikova G, Joshi P, Stoddart CA (2012) Impaired surfactant production by alveolar epithelial cells in a SCID-hu lung mouse model of congenital human cytomegalovirus infection. J Virol 86(23):12795–12805. doi:10.1128/jvi.01054-12
68. Gross NJ, Smith DM (1981) Impaired surfactant phospholipid metabolism in hyperoxic mouse lungs. J Appl Physiol Respir Environ Exerc Physiol 51(5):1198–1203
69. Martinez Sarrasague M, Cimato A, Rubin de Celis E, Facorro G (2011) Influence of serum protein and albumin addition on the structure and activity of an exogenous pulmonary surfactant. Respir Physiol Neurobiol 175(3):316–321. doi:10.1016/j.resp.2010.12.009
70. Cekic C, Linden J (2016) Purinergic regulation of the immune system. Nat Rev Immunol 16(3):177–192
71. Barletta KE, Ley K, Mehrad B (2012) Regulation of neutrophil function by adenosine. Arterioscler Thromb Vasc Biol 32(4):856–864. doi:10.1161/atvbaha.111.226845
72. Burnstock G (2012) Purinergic signalling: its unpopular beginning, its acceptance and its exciting future. BioEssays 34(3):218–225. doi:10.1002/bies.201100130
73. Cronstein BN, Daguma L, Nichols D, Hutchison AJ, Williams M (1990) The adenosine/neutrophil paradox resolved: human neutrophils possess both A1 and A2 receptors that promote chemotaxis and inhibit O2 generation, respectively. J Clin Invest 85(4):1150–1157. doi:10.1172/jci114547
74. Rose FR, Hirschhorn R, Weissmann G, Cronstein BN (1988) Adenosine promotes neutrophil chemotaxis. J Exp Med 167(3):1186–1194
75. Felsch A, Stocker K, Borchard U (1995) Phorbol ester-stimulated adherence of neutrophils to endothelial cells is reduced by adenosine A2 receptor agonists. J Immunol (Baltimore, Md: 1950) 155(1):333–338
76. Thiel M, Chouker A (1995) Acting via A2 receptors, adenosine inhibits the production of tumor necrosis factor-alpha of endotoxin-stimulated human polymorphonuclear leukocytes. J Lab Clin Med 126(3):275–282
77. Salmon JE, Cronstein BN (1990) Fc gamma receptor-mediated functions in neutrophils are modulated by adenosine receptor occupancy. A1 receptors are stimulatory and A2 receptors are inhibitory. J Immunol (Baltimore, Md: 1950) 145(7):2235–2240
78. Zalavary S, Stendahl O, Bengtsson T (1994) The role of cyclic AMP, calcium and filamentous actin in adenosine modulation of Fc receptor-mediated phagocytosis in human neutrophils. Biochim Biophys Acta 1222(2):249–256
79. Zalavary S, Bengtsson T (1998) Adenosine inhibits actin dynamics in human neutrophils: evidence for the involvement of cAMP. Eur J Cell Biol 75(2):128–139. doi:10.1016/s0171-9335(98)80055-1
80. Xu X, Zheng S, Xiong Y, Wang X, Qin W, Zhang H, Sun B (2017) Adenosine effectively restores endotoxin-induced inhibition of human neutrophil chemotaxis via A1 receptor-p38 pathway. Inflammation Res: Off J Eur Histamine Res Soc [et al] 66(4):353–364. doi:10.1007/s00011-016-1021-3
81. Chen L, Fredholm BB, Jondal M (2008) Adenosine, through the A1 receptor, inhibits vesicular MHC class I cross-presentation by resting DC. Mol Immunol 45(8):2247–2254. doi:10.1016/j.molimm.2007.11.016
82. Schnurr M, Toy T, Shin A, Hartmann G, Rothenfusser S, Soellner J, Davis ID, Cebon J, Maraskovsky E (2004) Role of adenosine receptors in regulating chemotaxis and cytokine production of plasmacytoid dendritic cells. Blood 103(4):1391–1397. doi:10.1182/blood-2003-06-1959
83. Figueiro F, Muller L, Funk S, Jackson EK, Battastini AM, Whiteside TL (2016) Phenotypic and functional characteristics of CD39high human regulatory B cells (Breg). Oncoimmunol 5(2):e1082703. doi:10.1080/2162402x.2015.1082703
84. Ohtsuka T, Changelian PS, Bouis D, Noon K, Harada H, Lama VN, Pinsky DJ (2010) Ecto-5′-nucleotidase (CD73) attenuates allograft airway rejection through adenosine 2A receptor stimulation. J Immunol (Baltimore, Md: 1950) 185(2):1321–1329. doi:10.4049/jimmunol.0901847
85. Link AA, Kino T, Worth JA, McGuire JL, Crane ML, Chrousos GP, Wilder RL, Elenkov IJ (2000) Ligand-activation of the adenosine A2a receptors inhibits IL-12 production by human monocytes. J Immunol (Baltimore, Md: 1950) 164(1):436–442
86. Zhang JG, Hepburn L, Cruz G, Borman RA, Clark KL (2005) The role of adenosine A2A and A2B receptors in the regulation of TNF-alpha production by human monocytes. Biochem Pharmacol 69(6):883–889. doi:10.1016/j.bcp.2004.12.008
87. Thiel M, Chambers JD, Chouker A, Fischer S, Zourelidis C, Bardenheuer HJ, Arfors KE, Peter K (1996) Effect of adenosine on the expression of beta(2) integrins and L-selectin of human polymorphonuclear leukocytes in vitro. J Leukoc Biol 59(5):671–682
88. Wollner A, Wollner S, Smith JB (1993) Acting via A2 receptors, adenosine inhibits the upregulation of Mac-1 (Cd11b/CD18) expression on FMLP-stimulated neutrophils. Am J Respir Cell Mol Biol 9(2):179–185. doi:10.1165/ajrcmb/9.2.179
89. Cadieux JS, Leclerc P, St-Onge M, Dussault AA, Laflamme C, Picard S, Ledent C, Borgeat P, Pouliot M (2005) Potentiation of neutrophil cyclooxygenase-2 by adenosine: an early anti-inflammatory signal. J Cell Sci 118(Pt 7):1437–1447. doi:10.1242/jcs.01737
90. Sullivan GW, Linden J, Buster BL, Scheld WM (1999) Neutrophil A2A adenosine receptor inhibits inflammation in a rat model of meningitis: synergy with the type IV phosphodiesterase inhibitor, rolipram. J Infect Dis 180(5):1550–1560. doi:10.1086/315084
91. McColl SR, St-Onge M, Dussault AA, Laflamme C, Bouchard L, Boulanger J, Pouliot M (2006) Immunomodulatory impact of the A2A adenosine receptor on the profile of chemokines produced by neutrophils. FASEB J: Off Publ Fed Am Soc Exp Biol 20(1):187–189. doi:10.1096/fj.05-4804fje
92. Krump E, Lemay G, Borgeat P (1996) Adenosine A2 receptor-induced inhibition of leukotriene B4 synthesis in whole blood ex vivo. Br J Pharmacol 117(8):1639–1644
93. Krump E, Picard S, Mancini J, Borgeat P (1997) Suppression of leukotriene B4 biosynthesis by endogenous adenosine in ligand-activated human neutrophils. J Exp Med 186(8):1401–1406
94. Surette ME, Krump E, Picard S, Borgeat P (1999) Activation of leukotriene synthesis in human neutrophils by exogenous arachidonic acid: inhibition by adenosine A(2a) receptor agonists and crucial role of autocrine activation by leukotriene B(4). Mol Pharmacol 56(5):1055–1062
95. Flamand N, Boudreault S, Picard S, Austin M, Surette ME, Plante H, Krump E, Vallee MJ, Gilbert C, Naccache P, Laviolette M, Borgeat P (2000) Adenosine, a potent natural suppressor of arachidonic acid release and leukotriene biosynthesis in human neutrophils. Am J Respir Crit Care Med 161(2 Pt 2):S88–S94. doi:10.1164/ajrccm.161.supplement_1.ltta-18
96. Flamand N, Surette ME, Picard S, Bourgoin S, Borgeat P (2002) Cyclic AMP-mediated inhibition of 5-lipoxygenase translocation and leukotriene biosynthesis in human neutrophils. Mol Pharmacol 62(2):250–256
97. Sullivan GW, Rieger JM, Scheld WM, Macdonald TL, Linden J (2001) Cyclic AMP-dependent inhibition of human neutrophil oxidative activity by substituted 2-propynylcyclohexyl adenosine A(2A) receptor agonists. Br J Pharmacol 132(5):1017–1026. doi:10.1038/sj.bjp.0703893
98. Anderson R, Visser SS, Ramafi G, Theron AJ (2000) Accelerated resequestration of cytosolic calcium and suppression of the pro-inflammatory activities of human neutrophils by CGS 21680 in vitro. Br J Pharmacol 130(4):717–724. doi:10.1038/sj.bjp.0703344
99. Richter J (1992) Effect of adenosine analogues and cAMP-raising agents on TNF-, GM-CSF-, and chemotactic peptide-induced degranulation in single adherent neutrophils. J Leukoc Biol 51(3):270–275
100. Visser SS, Theron AJ, Ramafi G, Ker JA, Anderson R (2000) Apparent involvement of the A(2A) subtype adenosine receptor in the anti-inflammatory interactions of CGS 21680, cyclopentyladenosine, and IB-MECA with human neutrophils. Biochem Pharmacol 60(7):993–999
101. Walker BA, Rocchini C, Boone RH, Ip S, Jacobson MA (1997) Adenosine A2a receptor activation delays apoptosis in human neutrophils. J Immunol (Baltimore, Md: 1950) 158(6):2926–2931
102. Liu YW, Yang T, Zhao L, Ni Z, Yang N, He F, Dai SS (2016) Activation of adenosine 2A receptor inhibits neutrophil apoptosis in an autophagy-dependent manner in mice with systemic inflammatory response syndrome. Sci Report 6:33614. doi:10.1038/srep33614
103. Ryzhov S, Goldstein AE, Matafonov A, Zeng D, Biaggioni I, Feoktistov I (2004) Adenosine-activated mast cells induce IgE synthesis by B lymphocytes: an A2B-mediated process involving Th2 cytokines IL-4 and IL-13 with implications for asthma. J Immunol (Baltimore, Md: 1950) 172(12):7726–7733
104. Kreckler LM, Gizewski E, Wan TC, Auchampach JA (2009) Adenosine suppresses lipopolysaccharide-induced tumor necrosis factor-alpha production by murine macrophages through a protein kinase A and exchange protein activated by cAMP-independent signaling pathway. J Pharmacol Exp Ther 331(3):1051–1061. doi:10.1124/jpet.109.157651
105. Hassanian SM, Dinarvand P, Rezaie AR (2014) Adenosine regulates the proinflammatory signaling function of thrombin in endothelial cells. J Cell Physiol 229(9):1292–1300. doi:10.1002/jcp.24568
106. Zarek PE, Huang CT, Lutz ER, Kowalski J, Horton MR, Linden J, Drake CG, Powell JD (2008) A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells. Blood 111(1):251–259. doi:10.1182/blood-2007-03-081646
107. Csoka B, Himer L, Selmeczy Z, Vizi ES, Pacher P, Ledent C, Deitch EA, Spolarics Z, Nemeth ZH, Hasko G (2008) Adenosine A2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function. FASEB J: Off Publ Fed Am Soc Exp Biol 22(10):3491–3499. doi:10.1096/fj.08-107458
108. Alam MS, Kurtz CC, Wilson JM, Burnette BR, Wiznerowicz EB, Ross WG, Rieger JM, Figler RA, Linden J, Crowe SE, Ernst PB (2009) A2A adenosine receptor (AR) activation inhibits pro-inflammatory cytokine production by human CD4+ helper T cells and regulates Helicobacter-induced gastritis and bacterial persistence. Mucosal Immunol 2(3):232–242. doi:10.1038/mi.2009.4
109. Hasko G, Kuhel DG, Chen JF, Schwarzschild MA, Deitch EA, Mabley JG, Marton A, Szabo C (2000) Adenosine inhibits IL-12 and TNF-[alpha] production via adenosine A2a receptor-dependent and independent mechanisms. FASEB J: Off Publ Fed Am Soc Exp Biol 14(13):2065–2074. doi:10.1096/fj.99-0508com
110. Erdmann AA, Gao ZG, Jung U, Foley J, Borenstein T, Jacobson KA, Fowler DH (2005) Activation of Th1 and Tc1 cell adenosine A2A receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo. Blood 105(12):4707–4714. doi:10.1182/blood-2004-04-1407
111. Lappas CM, Rieger JM, Linden J (2005) A2A adenosine receptor induction inhibits IFN-gamma production in murine CD4+ T cells. J Immunol (Baltimore, Md: 1950) 174(2):1073–1080
112. Ohta A, Kini R, Ohta A, Subramanian M, Madasu M, Sitkovsky M (2012) The development and immunosuppressive functions of CD4(+) CD25(+) FoxP3(+) regulatory T cells are under influence of the adenosine-A2A adenosine receptor pathway. Front Immunol 3:190. doi:10.3389/fimmu.2012.00190
113. Huang X, He Y, Chen Y, Wu P, Gui D, Cai H, Chen A, Chen M, Dai C, Yao D, Wang L (2016) Baicalin attenuates bleomycin-induced pulmonary fibrosis via adenosine A2a receptor related TGF-beta1-induced ERK1/2 signaling pathway. BMC Pulm Med 16(1):132. doi:10.1186/s12890-016-0294-1
114. Barbera-Cremades M, Baroja-Mazo A, Pelegrin P (2016) Purinergic signaling during macrophage differentiation results in M2 alternative activated macrophages. J Leukoc Biol 99(2):289–299. doi:10.1189/jlb.1A0514-267RR
115. Csoka B, Selmeczy Z, Koscso B, Nemeth ZH, Pacher P, Murray PJ, Kepka-Lenhart D, Morris SM Jr, Gause WC, Leibovich SJ, Hasko G (2012) Adenosine promotes alternative macrophage activation via A2A and A2B receptors. FASEB J: Off Publ Fed Am Soc Exp Biol 26(1):376–386. doi:10.1096/fj.11-190934
116. Ferrante CJ, Pinhal-Enfield G, Elson G, Cronstein BN, Hasko G, Outram S, Leibovich SJ (2013) The adenosine-dependent angiogenic switch of macrophages to an M2-like phenotype is independent of interleukin-4 receptor alpha (IL-4Ralpha) signaling. Inflammation 36(4):921–931. doi:10.1007/s10753-013-9621-3
117. Koscso B, Csoka B, Kokai E, Nemeth ZH, Pacher P, Virag L, Leibovich SJ, Hasko G (2013) Adenosine augments IL-10-induced STAT3 signaling in M2c macrophages. J Leukoc Biol 94(6):1309–1315. doi:10.1189/jlb.0113043
118. Hasko G, Pacher P (2012) Regulation of macrophage function by adenosine. Arterioscler Thromb Vasc Biol 32(4):865–869. doi:10.1161/atvbaha.111.226852
119. Koroskenyi K, Kiss B, Szondy Z (2016) Adenosine A2A receptor signaling attenuates LPS-induced pro-inflammatory cytokine formation of mouse macrophages by inducing the expression of DUSP1. Biochimica et biophysica acta 1863 (7 Pt A):1461-1471. doi:10.1016/j.bbamcr.2016.04.003
120. Majumdar S, Aggarwal BB (2003) Adenosine suppresses activation of nuclear factor-kappaB selectively induced by tumor necrosis factor in different cell types. Oncogene 22(8):1206–1218. doi:10.1038/sj.onc.1206184
121. Mirakaj V, Thix CA, Laucher S, Mielke C, Morote-Garcia JC, Schmit MA, Henes J, Unertl KE, Kohler D, Rosenberger P (2010) Netrin-1 dampens pulmonary inflammation during acute lung injury. Am J Respir Crit Care Med 181(8):815–824. doi:10.1164/rccm.200905-0717OC
122. Aherne CM, Collins CB, Masterson JC, Tizzano M, Boyle TA, Westrich JA, Parnes JA, Furuta GT, Rivera-Nieves J, Eltzschig HK (2012) Neuronal guidance molecule netrin-1 attenuates inflammatory cell trafficking during acute experimental colitis. Gut 61(5):695–705. doi:10.1136/gutjnl-2011-300012
123. van der Hoeven D, Wan TC, Gizewski ET, Kreckler LM, Maas JE, Van Orman J, Ravid K, Auchampach JA (2011) A role for the low-affinity A2B adenosine receptor in regulating superoxide generation by murine neutrophils. J Pharmacol Exp Ther 338(3):1004–1012. doi:10.1124/jpet.111.181792
124. Nemeth ZH, Lutz CS, Csoka B, Deitch EA, Leibovich SJ, Gause WC, Tone M, Pacher P, Vizi ES, Hasko G (2005) Adenosine augments IL-10 production by macrophages through an A2B receptor-mediated posttranscriptional mechanism. J Immunol (Baltimore, Md: 1950) 175(12):8260–8270
125. Novitskiy SV, Ryzhov S, Zaynagetdinov R, Goldstein AE, Huang Y, Tikhomirov OY, Blackburn MR, Biaggioni I, Carbone DP, Feoktistov I, Dikov MM (2008) Adenosine receptors in regulation of dendritic cell differentiation and function. Blood 112(5):1822–1831. doi:10.1182/blood-2008-02-136325
126. Wilson JM, Kurtz CC, Black SG, Ross WG, Alam MS, Linden J, Ernst PB (2011) The A2B adenosine receptor promotes Th17 differentiation via stimulation of dendritic cell IL-6. J Immunol (Baltimore, Md: 1950) 186(12):6746–6752. doi:10.4049/jimmunol.1100117
127. Liang D, Zuo A, Shao H, Chen M, Kaplan HJ, Sun D (2015) A2B adenosine receptor activation switches differentiation of bone marrow cells to a CD11c(+)Gr-1(+) dendritic cell subset that promotes the Th17 response. Immun Inflammation Dis 3(4):360–373. doi:10.1002/iid3.74
128. Karmouty-Quintana H, Philip K, Acero LF, Chen NY, Weng T, Molina JG, Luo F, Davies J, Le NB, Bunge I, Volcik KA, Le TT, Johnston RA, Xia Y, Eltzschig HK, Blackburn MR (2015) Deletion of ADORA2B from myeloid cells dampens lung fibrosis and pulmonary hypertension. FASEB J: Off Publ Fed Am Soc Exp Biol 29(1):50–60. doi:10.1096/fj.14-260182
129. Eckle T, Grenz A, Laucher S, Eltzschig HK (2008) A2B adenosine receptor signaling attenuates acute lung injury by enhancing alveolar fluid clearance in mice. J Clin Invest 118(10):3301–3315
130. Grant MB, Tarnuzzer RW, Caballero S, Ozeck MJ, Davis MI, Spoerri PE, Feoktistov I, Biaggioni I, Shryock JC, Belardinelli L (1999) Adenosine receptor activation induces vascular endothelial growth factor in human retinal endothelial cells. Circ Res 85(8):699–706
131. Zhong H, Wu Y, Belardinelli L, Zeng D (2006) A2B adenosine receptors induce IL-19 from bronchial epithelial cells, resulting in TNF-alpha increase. Am J Respir Cell Mol Biol 35(5):587–592. doi:10.1165/rcmb.2005-0476OC
132. Wilkinson PF, Farrell FX, Morel D, Law W, Murphy S (2016) Adenosine signaling increases proinflammatory and profibrotic mediators through activation of a functional adenosine 2B receptor in renal fibroblasts. Ann Clin Lab Sci 46(4):339–345
133. Feoktistov I, Ryzhov S, Goldstein AE, Biaggioni I (2003) Mast cell-mediated stimulation of angiogenesis: cooperative interaction between A2B and A3 adenosine receptors. Circ Res 92(5):485–492. doi:10.1161/01.res.0000061572.10929.2d
134. Chen Y, Corriden R, Inoue Y, Yip L, Hashiguchi N, Zinkernagel A, Nizet V, Insel PA, Junger WG (2006) ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors. Science 314(5806):1792–1795
135. 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 (Augusta, Ga) 30(2):173–177. doi:10.1097/shk.0b013e318160dad4
136. Tweedy L, Knecht DA, Mackay GM, Insall RH (2016) Self-generated chemoattractant gradients: attractant depletion extends the range and robustness of chemotaxis. PLoS Biol 14(3):e1002404. doi:10.1371/journal.pbio.1002404
137. Tweedy L, Susanto O, Insall RH (2016) Self-generated chemotactic gradients-cells steering themselves. Curr Opin Cell Biol 42:46–51. doi:10.1016/j.ceb.2016.04.003
138. Dona E, Barry JD, Valentin G, Quirin C, Khmelinskii A, Kunze A, Durdu S, Newton LR, Fernandez-Minan A, Huber W, Knop M, Gilmour D (2013) Directional tissue migration through a self-generated chemokine gradient. Nature 503(7475):285–289. doi:10.1038/nature12635
139. So H (2016) Where to go: breaking the symmetry in cell motility. PLoS Biol 14(5):e1002463. doi:10.1371/journal.pbio.1002463
140. Moissoglu K, Majumdar R, Parent CA (2014) Cell migration: sinking in a gradient. Curr Biol: CB 24(1):R23–R25. doi:10.1016/j.cub.2013.10.075
141. Joos G, Jakim J, Kiss B, Szamosi R, Papp T, Felszeghy S, Saghy T, Nagy G, Szondy Z (2017) Involvement of adenosine A3 receptors in the chemotactic navigation of macrophages towards apoptotic cells. Immunol Lett 183:62–72. doi:10.1016/j.imlet.2017.02.002
142. Lee JY, Jhun BS, Oh YT, Lee JH, Choe W, Baik HH, Ha J, Yoon KS, Kim SS, Kang I (2006) Activation of adenosine A3 receptor suppresses lipopolysaccharide-induced TNF-alpha production through inhibition of PI 3-kinase/Akt and NF-kappaB activation in murine BV2 microglial cells. Neurosci Lett 396(1):1–6. doi:10.1016/j.neulet.2005.11.004
143. Ren T, Qiu Y, Wu W, Feng X, Ye S, Wang Z, Tian T, He Y, Yu C, Zhou Y (2014) Activation of adenosine A3 receptor alleviates TNF-alpha-induced inflammation through inhibition of the NF-kappaB signaling pathway in human colonic epithelial cells. Mediat Inflamm 2014:818251. doi:10.1155/2014/818251
144. Hoskin DW, Butler JJ, Drapeau D, Haeryfar SM, Blay J (2002) Adenosine acts through an A3 receptor to prevent the induction of murine anti-CD3-activated killer T cells. Int J Cancer 99(3):386–395. doi:10.1002/ijc.10325
145. Morschl E, Molina JG, Volmer JB, Mohsenin A, Pero RS, Hong JS, Kheradmand F, Lee JJ, Blackburn MR (2008) A3 adenosine receptor signaling influences pulmonary inflammation and fibrosis. Am J Respir Cell Mol Biol 39(6):697–705. doi:10.1165/rcmb.2007-0419OC
146. Oury C, Lecut C, Hego A, Wera O, Delierneux C (2015) Purinergic control of inflammation and thrombosis: role of P2X1 receptors. Comput Struct Biotechnol J 13:106–110. doi:10.1016/j.csbj.2014.11.008
147. Woehrle T, Yip L, Elkhal A, Sumi Y, Chen Y, Yao Y, Insel PA, Junger WG (2010) Pannexin-1 hemichannel-mediated ATP release together with P2X1 and P2X4 receptors regulate T-cell activation at the immune synapse. Blood 116(18):3475–3484. doi:10.1182/blood-2010-04-277707
148. Bulanova E, Budagian V, Orinska Z, Koch-Nolte F, Haag F, Bulfone-Paus S (2009) ATP induces P2X7 receptor-independent cytokine and chemokine expression through P2X1 and P2X3 receptors in murine mast cells (article retracted in 2011 due to figure irregularities). J Leukoc Biol 85(4):692–702. doi:10.1189/jlb.0808470
149. Manohar M, Hirsh MI, Chen Y, Woehrle T, Karande AA, Junger WG (2012) ATP release and autocrine signaling through P2X4 receptors regulate gammadelta T cell activation. J Leukoc Biol 92(4):787–794. doi:10.1189/jlb.0312121
150. Vazquez-Villoldo N, Domercq M, Martin A, Llop J, Gomez-Vallejo V, Matute C (2014) P2X4 receptors control the fate and survival of activated microglia. Glia 62(2):171–184. doi:10.1002/glia.22596
151. Lee BH, Hwang DM, Palaniyar N, Grinstein S, Philpott DJ, Hu J (2012) Activation of P2X(7) receptor by ATP plays an important role in regulating inflammatory responses during acute viral infection. PLoS One 7(4):e35812. doi:10.1371/journal.pone.0035812
152. Jo EK, Kim JK, Shin DM, Sasakawa C (2016) Molecular mechanisms regulating NLRP3 inflammasome activation. Cell Mol Immunol 13(2):148–159
153. Latz E, Xiao TS, Stutz A (2013) Activation and regulation of the inflammasomes. Nat Rev Immunol 13(6):397–411. doi:10.1038/nri3452
154. Sakaki H, Fujiwaki T, Tsukimoto M, Kawano A, Harada H, Kojima S (2013) P2X4 receptor regulates P2X7 receptor-dependent IL-1beta and IL-18 release in mouse bone marrow-derived dendritic cells. Biochem Biophys Res Commun 432(3):406–411. doi:10.1016/j.bbrc.2013.01.135
155. Luna-Gomes T, Santana PT, Coutinho-Silva R (2015) Silica-induced inflammasome activation in macrophages: role of ATP and P2X7 receptor. Immunobiology 220(9):1101–1106. doi:10.1016/j.imbio.2015.05.004
156. Karmakar M, Katsnelson MA, Dubyak GR, Pearlman E (2016) Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1beta secretion in response to ATP. Nat Commun 7:10555. doi:10.1038/ncomms10555
157. Eleftheriadis T, Pissas G, Karioti A, Antoniadi G, Golfinopoulos S, Liakopoulos V, Mamara A, Speletas M, Koukoulis G, Stefanidis I (2013) Uric acid induces caspase-1 activation, IL-1beta secretion and P2X7 receptor dependent proliferation in primary human lymphocytes. Hippokratia 17(2):141–145
158. Tsukimoto M, Maehata M, Harada H, Ikari A, Takagi K, Degawa M (2006) P2X7 receptor-dependent cell death is modulated during murine T cell maturation and mediated by dual signaling pathways. J Immunol (Baltimore, Md: 1950) 177(5):2842–2850
159. 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. doi:10.1016/j.cellimm.2006.12.003
160. Scheuplein F, Schwarz N, Adriouch S, Krebs C, Bannas P, Rissiek B, Seman M, Haag F, Koch-Nolte F (2009) NAD+ and ATP released from injured cells induce P2X7-dependent shedding of CD62L and externalization of phosphatidylserine by murine T cells. J Immunol (Baltimore, Md: 1950) 182(5):2898–2908. doi:10.4049/jimmunol.0801711
161. Kawano A, Tsukimoto M, Noguchi T, Hotta N, Harada H, Takenouchi T, Kitani H, Kojima S (2012) Involvement of P2X4 receptor in P2X7 receptor-dependent cell death of mouse macrophages. Biochem Biophys Res Commun 419(2):374–380. doi:10.1016/j.bbrc.2012.01.156
162. Gu BJ, Wiley JS (2006) Rapid ATP-induced release of matrix metalloproteinase 9 is mediated by the P2X7 receptor. Blood 107(12):4946–4953. doi:10.1182/blood-2005-07-2994
163. de Torre-Minguela C, Barbera-Cremades M, Gomez AI, Martin-Sanchez F, Pelegrin P (2016) Macrophage activation and polarization modify P2X7 receptor secretome influencing the inflammatory process. Sci Report 6:22586. doi:10.1038/srep22586
164. 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: Off Publ Fed Am Soc Exp Biol 29(9):3626–3637. doi:10.1096/fj.15-272450
165. Wareham KJ, Seward EP (2016) P2X7 receptors induce degranulation in human mast cells. Purinergic Signal 12(2):235–246. doi:10.1007/s11302-016-9497-4
166. Kawamura H, Aswad F, Minagawa M, Govindarajan S, Dennert G (2006) P2X7 receptors regulate NKT cells in autoimmune hepatitis. J Immunol (Baltimore, Md: 1950) 176(4):2152–2160
167. Pupovac A, Foster CM, Sluyter R (2013) Human P2X7 receptor activation induces the rapid shedding of CXCL16. Biochem Biophys Res Commun 432(4):626–631. doi:10.1016/j.bbrc.2013.01.134
168. Pupovac A, Geraghty NJ, Watson D, Sluyter R (2015) Activation of the P2X7 receptor induces the rapid shedding of CD23 from human and murine B cells. Immunol Cell Biol 93(1):77–85. doi:10.1038/icb.2014.69
169. Huang SW, Walker C, Pennock J, Else K, Muller W, Daniels MJ, Pellegrini C, Brough D, Lopez-Castejon G, Cruickshank SM (2016) P2X7 receptor-dependent tuning of gut epithelial responses to infection. Immunol Cell BiolImmunology and cell biology. doi:10.1038/icb.2016.75
170. Yip L, Woehrle T, Corriden R, Hirsh M, Chen Y, Inoue Y, Ferrari V, Insel PA, Junger WG (2009) Autocrine regulation of T-cell activation by ATP release and P2X7 receptors. FASEB J: Off Publ Fed Am Soc Exp Biol 23(6):1685–1693. doi:10.1096/fj.08-126458
171. Proietti M, Cornacchione V, Rezzonico Jost T, Romagnani A, Faliti CE, Perruzza L, Rigoni R, Radaelli E, Caprioli F, Preziuso S, Brannetti B, Thelen M, McCoy KD, Slack E, Traggiai E, Grassi F (2014) ATP-gated ionotropic P2X7 receptor controls follicular T helper cell numbers in Peyer’s patches to promote host-microbiota mutualism. Immunity 41(5):789–801. doi:10.1016/j.immuni.2014.10.010
172. Hubert S, Rissiek B, Klages K, Huehn J, Sparwasser T, Haag F, Koch-Nolte F, Boyer O, Seman M, Adriouch S (2010) Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. J Exp Med 207(12):2561–2568. doi:10.1084/jem.20091154
173. Wilhelm K, Ganesan J, Muller T, Durr C, Grimm M, Beilhack A, Krempl CD, Sorichter S, Gerlach UV, Juttner E, Zerweck A, Gartner F, Pellegatti P, Di Virgilio F, Ferrari D, Kambham N, Fisch P, Finke J, Idzko M, Zeiser R (2010) Graft-versus-host disease is enhanced by extracellular ATP activating P2X7R. Nat Med 16(12):1434–1438. doi:10.1038/nm.2242
174. Mishra A, Guo Y, Zhang L, More S, Weng T, Chintagari NR, Huang C, Liang Y, Pushparaj S, Gou D, Breshears M, Liu L (2016) A critical role for P2X7 receptor-induced VCAM-1 shedding and neutrophil infiltration during acute lung injury. J Immunol
175. Wang CM, Chang YY, Sun SH (2003) Activation of P2X7 purinoceptor-stimulated TGF-beta 1 mRNA expression involves PKC/MAPK signalling pathway in a rat brain-derived type-2 astrocyte cell line, RBA-2. Cell Signal 15(12):1129–1137
176. Qu LP, Xue H, Yuan P, Zhou L, Yao T, Huang Y, Lu LM (2009) Adenosine 5′-triphosphate stimulates the increase of TGF-beta1 in rat mesangial cells under high-glucose conditions via reactive oxygen species and ERK1/2. Acta Pharmacol Sin 30(12):1601–1606. doi:10.1038/aps.2009.155
177. Nylander S, Mattsson C, Ramstrom S, Lindahl TL (2004) Synergistic action between inhibition of P2Y12/P2Y1 and P2Y12/thrombin in ADP- and thrombin-induced human platelet activation. Br J Pharmacol 142(8):1325–1331. doi:10.1038/sj.bjp.0705885
178. Muller T, Fay S, Vieira RP, Karmouty-Quintana H, Cicko S, Ayata K, Zissel G, Goldmann T, Lungarella G, Ferrari D, Di Virgilio F, Robaye B, Boeynaems JM, Blackburn MR, Idzko M (2017) The purinergic receptor subtype P2Y2 mediates chemotaxis of neutrophils and fibroblasts in fibrotic lung disease. Oncotarget. doi:10.18632/oncotarget.16414
179. 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. doi:10.1111/j.1398-9995.2010.02426.x
180. Vanderstocken G, Bondue B, Horckmans M, Di Pietrantonio L, Robaye B, Boeynaems JM, Communi D (2010) P2Y2 receptor regulates VCAM-1 membrane and soluble forms and eosinophil accumulation during lung inflammation. J Immunol (Baltimore, Md: 1950) 185(6):3702–3707. doi:10.4049/jimmunol.0903908
181. Ohsawa K, Irino Y, Nakamura Y, Akazawa C, Inoue K, Kohsaka S (2007) Involvement of P2X4 and P2Y12 receptors in ATP-induced microglial chemotaxis. Glia 55(6):604–616. doi:10.1002/glia.20489
182. Irino Y, Nakamura Y, Inoue K, Kohsaka S, Ohsawa K (2008) Akt activation is involved in P2Y12 receptor-mediated chemotaxis of microglia. J Neurosci Res 86(7):1511–1519. doi:10.1002/jnr.21610
183. Sil P, Hayes CP, Reaves BJ, Breen P, Quinn S, Sokolove J, Rada B (2017) P2Y6 receptor antagonist MRS2578 inhibits neutrophil activation and aggregated neutrophil extracellular trap formation induced by gout-associated monosodium urate crystals. J Immunol (Baltimore, Md: 1950) 198(1):428–442. doi:10.4049/jimmunol.1600766
184. Uratsuji H, Tada Y, Kawashima T, Kamata M, Hau CS, Asano Y, Sugaya M, Kadono T, Asahina A, Sato S, Tamaki K (2012) P2Y6 receptor signaling pathway mediates inflammatory responses induced by monosodium urate crystals. J Immunol (Baltimore, Md: 1950) 188(1):436–444. doi:10.4049/jimmunol.1003746
185. Kimura T, Kobayashi S, Hanihara-Tatsuzawa F, Sayama A, MaruYama T, Muta T (2014) Responses of macrophages to the danger signals released from necrotic cells. Int Immunol 26(12):697–704. doi:10.1093/intimm/dxu080
186. Inoue K (2007) UDP facilitates microglial phagocytosis through P2Y6 receptors. Cell Adhes Migr 1(3):131–132
187. Morioka N, Tokuhara M, Harano S, Nakamura Y, Hisaoka-Nakashima K, Nakata Y (2013) The activation of P2Y6 receptor in cultured spinal microglia induces the production of CCL2 through the MAP kinases-NF-kappaB pathway. Neuropharmacology 75:116–125. doi:10.1016/j.neuropharm.2013.07.017
188. Xu Y, Hu W, Liu Y, Xu P, Li Z, Wu R, Shi X, Tang Y (2016) P2Y6 receptor-mediated microglial phagocytosis in radiation-induced brain injury. Mol Neurobiol 53(6):3552–3564. doi:10.1007/s12035-015-9282-3
189. Zhu J, Wang Z, Zhang N, Ma J, Xu SL, Wang Y, Shen Y, Li YH (2016) Protein interacting C-kinase 1 modulates surface expression of P2Y6 purinoreceptor, actin polymerization and phagocytosis in microglia. Neurochem Res 41(4):795–803. doi:10.1007/s11064-015-1754-3
190. Nakano M, Ito K, Yuno T, Soma N, Aburakawa S, Kasai K, Nakamura T, Takami H (2017) UDP/P2Y6 receptor signaling regulates IgE-dependent degranulation in human basophils. Allergol Int: Off J Jpn Soc Allergol. doi:10.1016/j.alit.2017.02.014
191. Khine AA, Del Sorbo L, Vaschetto R, Voglis S, Tullis E, Slutsky AS, Downey GP, Zhang H (2006) Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway. Blood 107(7):2936–2942. doi:10.1182/blood-2005-06-2314
192. Grbic DM, Degagne E, Larrivee JF, Bilodeau MS, Vinette V, Arguin G, Stankova J, Gendron FP (2012) P2Y6 receptor contributes to neutrophil recruitment to inflamed intestinal mucosa by increasing CXC chemokine ligand 8 expression in an AP-1-dependent manner in epithelial cells. Inflamm Bowel Dis 18(8):1456–1469. doi:10.1002/ibd.21931
193. Li R, Tan B, Yan Y, Ma X, Zhang N, Zhang Z, Liu M, Qian M, Du B (2014) Extracellular UDP and P2Y6 function as a danger signal to protect mice from vesicular stomatitis virus infection through an increase in IFN-beta production. J Immunol (Baltimore, Md: 1950) 193(9):4515–4526. doi:10.4049/jimmunol.1301930
194. Vaughan KR, Stokes L, Prince LR, Marriott HM, Meis S, Kassack MU, Bingle CD, Sabroe I, Surprenant A, Whyte MK (2007) Inhibition of neutrophil apoptosis by ATP is mediated by the P2Y11 receptor. J Immunol (Baltimore, Md: 1950) 179(12):8544–8553
195. Alkayed F, Kashimata M, Koyama N, Hayashi T, Tamura Y, Azuma Y (2012) P2Y11 purinoceptor mediates the ATP-enhanced chemotactic response of rat neutrophils. J Pharmacol Sci 120(4):288–295
196. van der Weyden L, Conigrave AD, Morris MB (2000) Signal transduction and white cell maturation via extracellular ATP and the P2Y11 receptor. Immunol Cell Biol 78(4):369–374. doi:10.1046/j.1440-1711.2000.00918.x
197. Wilkin F, Duhant X, Bruyns C, Suarez-Huerta N, Boeynaems JM, Robaye B (2001) The P2Y11 receptor mediates the ATP-induced maturation of human monocyte-derived dendritic cells. J Immunol (Baltimore, Md: 1950) 166(12):7172–7177
198. Schnurr M, Toy T, Stoitzner P, Cameron P, Shin A, Beecroft T, Davis ID, Cebon J, Maraskovsky E (2003) ATP gradients inhibit the migratory capacity of specific human dendritic cell types: implications for P2Y11 receptor signaling. Blood 102(2):613–620. doi:10.1182/blood-2002-12-3745
199. Meis S, Hamacher A, Hongwiset D, Marzian C, Wiese M, Eckstein N, Royer HD, Communi D, Boeynaems JM, Hausmann R, Schmalzing G, Kassack MU (2010) NF546 [4,4′-(carbonylbis(imino-3,1-phenylene-carbonylimino-3,1-(4-methyl-phenylene)-car bonylimino))-bis(1,3-xylene-alpha,alpha′-diphosphonic acid) tetrasodium salt] is a non-nucleotide P2Y11 agonist and stimulates release of interleukin-8 from human monocyte-derived dendritic cells. J Pharmacol Exp Ther 332(1):238–247. doi:10.1124/jpet.109.157750
200. Sakaki H, Tsukimoto M, Harada H, Moriyama Y, Kojima S (2013) Autocrine regulation of macrophage activation via exocytosis of ATP and activation of P2Y11 receptor. PLoS One 8(4):e59778. doi:10.1371/journal.pone.0059778
201. Satonaka H, Nagata D, Takahashi M, Kiyosue A, Myojo M, Fujita D, Ishimitsu T, Nagano T, Nagai R, Hirata Y (2015) Involvement of P2Y12 receptor in vascular smooth muscle inflammatory changes via MCP-1 upregulation and monocyte adhesion. Am J Phys Heart Circ Phys 308(8):H853–H861. doi:10.1152/ajpheart.00862.2013
202. Ben Addi A, 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 (Baltimore, Md: 1950) 185(10):5900–5906. doi:10.4049/jimmunol.0901799
203. Lou N, Takano T, Pei Y, Xavier AL, Goldman SA, Nedergaard M (2016) Purinergic receptor P2RY12-dependent microglial closure of the injured blood-brain barrier. Proc Natl Acad Sci U S A 113(4):1074–1079. doi:10.1073/pnas.1520398113
204. Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan WB, Julius D (2006) The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 9(12):1512–1519. doi:10.1038/nn1805
205. Moore CS, Ase AR, Kinsara A, Rao VT, Michell-Robinson M, Leong SY, Butovsky O, Ludwin SK, Seguela P, Bar-Or A, Antel JP (2015) P2Y12 expression and function in alternatively activated human microglia. Neurol(R) Neuroimmunol Neuroinflammation 2(2):e80. doi:10.1212/nxi.0000000000000080
206. Tozaki-Saitoh H, Miyata H, Yamashita T, Matsushita K, Tsuda M, Inoue K (2017) P2Y12 receptors in primary microglia activate nuclear factor of activated T-cell signaling to induce C-C chemokine 3 expression. J Neurochem 141(1):100–110. doi:10.1111/jnc.13968
207. Wang L, Olivecrona G, Götberg M, Olsson ML, Winzell MS, Erlinge D (2005) ADP acting on P2Y13 receptors is a negative feedback pathway for ATP release from human red blood cells. Circ Res 96(2):189–196. doi:10.1161/01.res.0000153670.07559.e4
208. Arase T, Uchida H, Kajitani T, Ono M, Tamaki K, Oda H, Nishikawa S, Kagami M, Nagashima T, Masuda H, Asada H, Yoshimura Y, Maruyama T (2009) The UDP-glucose receptor P2RY14 triggers innate mucosal immunity in the female reproductive tract by inducing IL-8. J Immunol (Baltimore, Md: 1950) 182(11):7074–7084. doi:10.4049/jimmunol.0900001
209. Barrett MO, Sesma JI, Ball CB, Jayasekara PS, Jacobson KA, Lazarowski ER, Harden TK (2013) A selective high-affinity antagonist of the P2Y14 receptor inhibits UDP-glucose-stimulated chemotaxis of human neutrophils. Mol Pharmacol 84(1):41–49. doi:10.1124/mol.113.085654
210. Burnstock G, Boeynaems JM (2014) Purinergic signalling and immune cells. Purinergic Signal 10(4):529–564. doi:10.1007/s11302-014-9427-2
211. 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
212. Eckle T, Fullbier L, Wehrmann M, Khoury J, Mittelbronn M, Ibla J, Rosenberger P, Eltzschig HK (2007) Identification of ectonucleotidases CD39 and CD73 in innate protection during acute lung injury. J Immunol 178(12):8127–8137
213. Matsuyama H, Amaya F, Hashimoto S, Ueno H, Beppu S, Mizuta M, Shime N, Ishizaka A, Hashimoto S (2008) Acute lung inflammation and ventilator-induced lung injury caused by ATP via the P2Y receptors: an experimental study. Respir Res 9:79
214. Csoka B, Nemeth ZH, Toro G, Koscso B, Kokai E, Robson SC, Enjyoji K, Rolandelli RH, Erdelyi K, Pacher P, Hasko G (2015) CD39 improves survival in microbial sepsis by attenuating systemic inflammation. FASEB J: Off Publ Fed Am Soc Exp Biol 29(1):25–36. doi:10.1096/fj.14-253567
215. Coddou C, Stojilkovic SS, Huidobro-Toro JP (2011) Allosteric modulation of ATP-gated P2X receptor channels. Rev Neurosci 22(3):335–354. doi:10.1515/rns.2011.014
216. Short KR, Kroeze EJ, Fouchier RA, Kuiken T (2014) Pathogenesis of influenza-induced acute respiratory distress syndrome. Lancet Infect Dis 14(1):57–69. doi:10.1016/s1473-3099(13)70286-x
217. Chen XJ, Seth S, Yue G, Kamat P, Compans RW, Guidot D, Brown LA, Eaton DC, Jain L (2004) Influenza virus inhibits ENaC and lung fluid clearance. Am J Physiol Lung Cell Mol Physiol 287(2):L366–L373. doi:10.1152/ajplung.00011.2004
218. Aeffner F, Bratasz A, Flano E, Powell KA, Davis IC (2012) Postinfection A77-1726 treatment improves cardiopulmonary function in H1N1 influenza-infected mice. Am J Respir Cell Mol Biol 47(4):543–551. doi:10.1165/rcmb.2012-0112OC
219. Wolk KE, Lazarowski ER, Traylor ZP, Yu EN, Jewell NA, Durbin RK, Durbin JE, Davis IC (2008) Influenza a virus inhibits alveolar fluid clearance in BALB/c mice. Am J Respir Crit Care Med 178(9):969–976. doi:10.1164/rccm.200803-455OC
220. Kunzelmann K, Sun J, Meanger J, King NJ, Cook DI (2007) Inhibition of airway Na+ transport by respiratory syncytial virus. J Virol 81(8):3714–3720. doi:10.1128/jvi.02621-06
221. Chen L, Song W, Davis IC, Shrestha K, Schwiebert E, Sullender WM, Matalon S (2009) Inhibition of Na+ transport in lung epithelial cells by respiratory syncytial virus infection. Am J Respir Cell Mol Biol 40(5):588–600. doi:10.1165/rcmb.2008-0034OC
222. Kunzelmann K, Konig J, Sun J, Markovich D, King NJ, Karupiah G, Young JA, Cook DI (2004) Acute effects of parainfluenza virus on epithelial electrolyte transport. J Biol Chem 279(47):48760–48766. doi:10.1074/jbc.M409747200
223. Shen BQ, Finkbeiner WE, Wine JJ, Mrsny RJ, Widdicombe JH (1994) Calu-3: a human airway epithelial cell line that shows cAMP-dependent Cl- secretion. Am J Phys 266(5 Pt 1):L493–L501
224. Airas L, Niemela J, Yegutkin G, Jalkanen S (2007) Mechanism of action of IFN-beta in the treatment of multiple sclerosis: a special reference to CD73 and adenosine. Ann N Y Acad Sci 1110:641–648. doi:10.1196/annals.1423.067
225. Niemela J, Ifergan I, Yegutkin GG, Jalkanen S, Prat A, Airas L (2008) IFN-beta regulates CD73 and adenosine expression at the blood-brain barrier. Eur J Immunol 38(10):2718–2726. doi:10.1002/eji.200838437
226. Kiss J, Yegutkin GG, Koskinen K, Savunen T, Jalkanen S, Salmi M (2007) IFN-beta protects from vascular leakage via up-regulation of CD73. Eur J Immunol 37(12):3334–3338. doi:10.1002/eji.200737793
227. Vignali DA, Collison LW, Workman CJ (2008) How regulatory T cells work. Nat Rev Immunol 8(7):523–532
228. Bauernfeind F, Bartok E, Rieger A, Franchi L, Nunez G, Hornung V (2011) Cutting edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome. J Immunol 187(2):613–617
229. Schroder K, Tschopp J (2010) The inflammasomes. Cell 140(6):821–832
230. Belete HA, Hubmayr RD, Wang S, Singh RD (2011) The role of purinergic signaling on deformation induced injury and repair responses of alveolar epithelial cells. PLoS One 6(11):e27469. doi:10.1371/journal.pone.0027469
231. Protti A, Cressoni M, Santini A, Langer T, Mietto C, Febres D, Chierichetti M, Coppola S, Conte G, Gatti S, Leopardi O, Masson S, Lombardi L, Lazzerini M, Rampoldi E, Cadringher P, Gattinoni L (2011) Lung stress and strain during mechanical ventilation: any safe threshold? Am J Respir Crit Care Med 183(10):1354–1362. doi:10.1164/rccm.201010-1757OC
232. Bellingan G, Maksimow M, Howell DC, Stotz M, Beale R, Beatty M, Walsh T, Binning A, Davidson A, Kuper M, Shah S, Cooper J, Waris M, Yegutkin GG, Jalkanen J, Salmi M, Piippo I, Jalkanen M, Montgomery H, Jalkanen S (2014) The effect of intravenous interferon-beta-1a (FP-1201) on lung CD73 expression and on acute respiratory distress syndrome mortality: an open-label study. Lancet Respir Med 2(2):98–107. doi:10.1016/s2213-2600(13)70259-5
233. Chunn JL, Molina JG, Mi T, Xia Y, Kellems RE, Blackburn MR (2005) Adenosine-dependent pulmonary fibrosis in adenosine deaminase-deficient mice. J Immunol (Baltimore, Md: 1950) 175(3):1937–1946
234. Chunn JL, Mohsenin A, Young HW, Lee CG, Elias JA, Kellems RE, Blackburn MR (2006) Partially adenosine deaminase-deficient mice develop pulmonary fibrosis in association with adenosine elevations. Am J Physiol Lung Cell Mol Physiol 290(3):L579–L587. doi:10.1152/ajplung.00258.2005
235. Nowrin K, Sohal SS, Peterson G, Patel R, Walters EH (2014) Epithelial-mesenchymal transition as a fundamental underlying pathogenic process in COPD airways: fibrosis, remodeling and cancer. Expert Rev Respir Med 8(5):547–559. doi:10.1586/17476348.2014.948853
236. Albert SP, DiRocco J, Allen GB, Bates JH, Lafollette R, Kubiak BD, Fischer J, Maroney S, Nieman GF (2009) The role of time and pressure on alveolar recruitment. J Appl Physiol (Bethesda, Md: 1985) 106(3):757–765. doi:10.1152/japplphysiol.90735.2008
237. Nieman G, Gatto LA, Marx W, Habashi N (2013) Is time the missing component in protective ventilation strategies? Crit Care Med 41(10):2461–2462. doi:10.1097/CCM.0b013e31828ce91b
238. Retamal J, Bergamini BC, Carvalho AR, Bozza FA, Borzone G, Borges JB, Larsson A, Hedenstierna G, Bugedo G, Bruhn A (2014) Non-lobar atelectasis generates inflammation and structural alveolar injury in the surrounding healthy tissue during mechanical ventilation. Crit Care 18(5):505. doi:10.1186/s13054-014-0505-1
239. Zhou Y, Schneider DJ, Morschl E, Song L, Pedroza M, Karmouty-Quintana H, Le T, Sun CX, Blackburn MR (2011) Distinct roles for the A2B adenosine receptor in acute and chronic stages of bleomycin-induced lung injury. J Immunol (Baltimore, Md: 1950) 186(2):1097–1106. doi:10.4049/jimmunol.1002907
240. Suki B, Stamenovic D, Hubmayr R (2011) Lung parenchymal mechanics. Comprehensive Physiology 1(3):1317–1351. doi:10.1002/cphy.c100033