Mechanisms of ATP Release by Inflammatory Cells

Michel Dosch, Joël Gerber, Fadi Jebbawi, Guido Beldi, Michel Dosch, Joël Gerber, Fadi Jebbawi, Guido Beldi

Abstract

Extracellular nucleotides (e.g., ATP, ADP, UTP, UDP) released by inflammatory cells interact with specific purinergic P2 type receptors to modulate their recruitment and activation. The focus of this review is on stimuli and mechanisms of extracellular nucleotide release and its consequences during inflammation. Necrosis leads to non-specific release of nucleotides, whereas specific release mechanisms include vesicular exocytosis and channel-mediated release via connexin or pannexin hemichannels. These release mechanisms allow stimulated inflammatory cells such as macrophages, neutrophils, and endothelial cells to fine-tune autocrine/paracrine responses during acute and chronic inflammation. Key effector functions of inflammatory cells are therefore regulated by purinergic signaling in acute and chronic diseases, making extracellular nucleotide release a promising target for the development of new therapies.

Keywords: ATP release; connexins; endothelial cells; extracellular nucleotides; inflammation; monocytes/macrophages; neutrophils; non-specific nucleotide release; pannexins; purinergic signaling; vesicular exocytosis.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
ATP release through vesicular exocytosis. (A) Active transport of ATP inside the vesicles through the vesicular nucleotide transporter (VNUT) using V-ATPase generated proton gradient (positive inside the vesicle) as a driving force; (B) SNARE zippering occurring spontaneously; (C) Increased intracellular calcium concentration leads to SNAREs mediated membrane fusion and release of ATP into the extracellular space.
Figure 2
Figure 2
ATP release through connexin-43 hemichannels. (A) Connexin-43 gating and structure. Gap26 and Gap27 are connexin-43 specific blockers that target extracellular loops, whereas Gap19 and CT9 target intracellular loops. Loop-tail interactions are represented by a double arrow; (B) Connexin-43 expression is induced in response to Toll-like receptor 4 agonist (LPS) and is dependent on ERK/AP-1 signaling in macrophages.
Figure 3
Figure 3
ATP release through pannexin-1 channels. (A) Pannexin-1 gating and structure. Caspase cleavage sites are located on the intracellular loop and the C-terminal tail; (B) Pannexin-1 channels activation via caspase-mediated cleavage [1]. The pore is plugged under homeostatic conditions and opens upon cleavage. Upon higher extracellular nucleotide concentration, activation of P2X7 receptor (P2X7R) leads to internalization of Pannexin-1 in terms of an autocrine negative feedback loop.

References

    1. Cekic C., Linden J. Purinergic regulation of the immune system. Nat. Rev. Immunol. 2016;16:177–192. doi: 10.1038/nri.2016.4.
    1. Idzko M., Ferrari D., Eltzschig H.K. Nucleotide signalling during inflammation. Nature. 2014;509:310–317. doi: 10.1038/nature13085.
    1. Trautmann A. Extracellular ATP in the immune system: More than just a “danger signal”. Sci. Signal. 2009;2:pe6. doi: 10.1126/scisignal.256pe6.
    1. Iyer S.S., Pulskens W.P., Sadler J.J., Butter L.M., Teske G.J., Ulland T.K., Eisenbarth S.C., Florquin S., Flavell R.A., Leemans J.C., et al. Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc. Natl. Acad. Sci. USA. 2009;106:20388–20393. doi: 10.1073/pnas.0908698106.
    1. Junger W.G. Immune cell regulation by autocrine purinergic signalling. Nat. Rev. Immunol. 2011;11:201–212. doi: 10.1038/nri2938.
    1. Di Virgilio F., Vuerich M. Purinergic signaling in the immune system. Auton. Neurosci. 2015;191:117–123. doi: 10.1016/j.autneu.2015.04.011.
    1. Burnstock G. Purinergic Signalling: Therapeutic Developments. Front. Pharmacol. 2017;8:661. doi: 10.3389/fphar.2017.00661.
    1. McDonald B., Pittman K., Menezes G.B., Hirota S.A., Slaba I., Waterhouse C.C., Beck P.L., Muruve D.A., Kubes P. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science. 2010;330:362–366. doi: 10.1126/science.1195491.
    1. Angus D.C., van der Poll T. Severe sepsis and septic shock. N. Engl. J. Med. 2013;369:840–851. doi: 10.1056/NEJMra1208623.
    1. Sumi Y., Woehrle T., Chen Y., Bao Y., Li X., Yao Y., Inoue Y., Tanaka H., Junger W.G. Plasma ATP is required for neutrophil activation in a mouse sepsis model. Shock. 2014;42:142–147. doi: 10.1097/SHK.0000000000000180.
    1. Li X., Kondo Y., Bao Y., Staudenmaier L., Lee A., Zhang J., Ledderose C., Junger W.G. Systemic Adenosine Triphosphate Impairs Neutrophil Chemotaxis and Host Defense in Sepsis. Crit. Care Med. 2017;45:e97–e104. doi: 10.1097/CCM.0000000000002052.
    1. Cauwels A., Rogge E., Vandendriessche B., Shiva S., Brouckaert P. Extracellular ATP drives systemic inflammation, tissue damage and mortality. Cell Death Dis. 2014;5:e1102. doi: 10.1038/cddis.2014.70.
    1. Ravichandran K.S. Beginnings of a good apoptotic meal: The find-me and eat-me signaling pathways. Immunity. 2011;35:445–455. doi: 10.1016/j.immuni.2011.09.004.
    1. Elliott M.R., Chekeni F.B., Trampont P.C., Lazarowski E.R., Kadl A., Walk S.F., Park D., Woodson R.I., Ostankovich M., Sharma P., et al. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature. 2009;461:282–286. doi: 10.1038/nature08296.
    1. Martens S., McMahon H.T. Mechanisms of membrane fusion: Disparate players and common principles. Nat. Rev. Mol. Cell Biol. 2008;9:543–556. doi: 10.1038/nrm2417.
    1. Moriyama Y., Hiasa M., Sakamoto S., Omote H., Nomura M. Vesicular nucleotide transporter (VNUT): Appearance of an actress on the stage of purinergic signaling. Purinergic Signal. 2017;13:387–404. doi: 10.1007/s11302-017-9568-1.
    1. Sawada K., Echigo N., Juge N., Miyaji T., Otsuka M., Omote H., Yamamoto A., Moriyama Y. Identification of a vesicular nucleotide transporter. Proc. Natl. Acad. Sci. USA. 2008;105:5683–5686. doi: 10.1073/pnas.0800141105.
    1. Miyaji T., Sawada K., Omote H., Moriyama Y. Divalent cation transport by vesicular nucleotide transporter. J. Biol. Chem. 2011;286:42881–42887. doi: 10.1074/jbc.M111.277269.
    1. Imura Y., Morizawa Y., Komatsu R., Shibata K., Shinozaki Y., Kasai H., Moriishi K., Moriyama Y., Koizumi S. Microglia release ATP by exocytosis. Glia. 2013;61:1320–1330. doi: 10.1002/glia.22517.
    1. Südhof T.C., Rothman J.E. Membrane fusion: Grappling with SNARE and SM proteins. Science. 2009;323:474–477. doi: 10.1126/science.1161748.
    1. Kato Y., Hiasa M., Ichikawa R., Hasuzawa N., Kadowaki A., Iwatsuki K., Shima K., Endo Y., Kitahara Y., Inoue T., et al. Identification of a vesicular ATP release inhibitor for the treatment of neuropathic and inflammatory pain. Proc. Natl. Acad. Sci. USA. 2017:201704847. doi: 10.1073/pnas.1704847114.
    1. Parzych K., Zetterqvist A.V., Wright W.R., Kirkby N.S., Mitchell J.A., Paul-Clark M.J. Differential role of pannexin-1/ATP/P2X7 axis in IL-1β release by human monocytes. FASEB J. 2017;31:2439–2445. doi: 10.1096/fj.201600256.
    1. Sáez P.J., Vargas P., Shoji K.F., Harcha P.A., Lennon-Duménil A.M., Sáez J.C. ATP promotes the fast migration of dendritic cells through the activity of pannexin 1 channels and P2X7 receptors. Sci. Signal. 2017;10 doi: 10.1126/scisignal.aah7107.
    1. Wang X., Qin W., Xu X., Xiong Y., Zhang Y., Zhang H., Sun B. Endotoxin-induced autocrine ATP signaling inhibits neutrophil chemotaxis through enhancing myosin light chain phosphorylation. Proc. Natl. Acad. Sci. USA. 2017;114:4483–4488. doi: 10.1073/pnas.1616752114.
    1. Zhang C., He H., Wang L., Zhang N., Huang H., Xiong Q., Yan Y., Wu N., Ren H., Han H., et al. Virus-Triggered ATP Release Limits Viral Replication through Facilitating IFN-β Production in a P2X7-Dependent Manner. J. Immunol. 2017;199:1372–1381. doi: 10.4049/jimmunol.1700187.
    1. Brown I.A., McClain J.L., Watson R.E., Patel B.A., Gulbransen B.D. Enteric glia mediate neuron death in colitis through purinergic pathways that require connexin-43 and nitric oxide. Cell. Mol. Gastroenterol. Hepatol. 2016;2:77–91. doi: 10.1016/j.jcmgh.2015.08.007.
    1. Qin J., Zhang G., Zhang X., Tan B., Lv Z., Liu M., Ren H., Qian M., Du B. TLR-Activated Gap Junction Channels Protect Mice against Bacterial Infection through Extracellular UDP Release. J. Immunol. 2016;196:1790–1798. doi: 10.4049/jimmunol.1501629.
    1. Lim To W.K., Kumar P., Marshall J.M. Hypoxia is an effective stimulus for vesicular release of ATP from human umbilical vein endothelial cells. Placenta. 2015;36:759–766. doi: 10.1016/j.placenta.2015.04.005.
    1. Lohman A.W., Leskov I.L., Butcher J.T., Johnstone S.R., Stokes T.A., Begandt D., DeLalio L.J., Best A.K., Penuela S., Leitinger N., et al. Pannexin 1 channels regulate leukocyte emigration through the venous endothelium during acute inflammation. Nat. Commun. 2015;6:7965. doi: 10.1038/ncomms8965.
    1. Chen Y., Bao Y., Zhang J., Woehrle T., Sumi Y., Ledderose S., Li X., Ledderose C., Junger W.G. Inhibition of Neutrophils by Hypertonic Saline Involves Pannexin-1, CD39, CD73, and Other Ectonucleotidases. Shock. 2015;44:221–227. doi: 10.1097/SHK.0000000000000402.
    1. Yang D., He Y., Muñoz-Planillo R., Liu Q., Núñez G. Caspase-11 Requires the Pannexin-1 Channel and the Purinergic P2X7 Pore to Mediate Pyroptosis and Endotoxic Shock. Immunity. 2015;43:923–932. doi: 10.1016/j.immuni.2015.10.009.
    1. Molica F., Morel S., Meens M.J., Denis J.F., Bradfield P.F., Penuela S., Zufferey A., Monyer H., Imhof B.A., Chanson M., et al. Functional role of a polymorphism in the Pannexin1 gene in collagen-induced platelet aggregation. Thromb. Haemost. 2015;114:325–336. doi: 10.1160/TH14-11-0981.
    1. Calder B.W., Matthew Rhett J., Bainbridge H., Fann S.A., Gourdie R.G., Yost M.J. Inhibition of connexin 43 hemichannel-mediated ATP release attenuates early inflammation during the foreign body response. Tissue Eng. Part A. 2015;21:1752–1762. doi: 10.1089/ten.tea.2014.0651.
    1. Csóka B., Németh Z.H., Törő G., Idzko M., Zech A., Koscsó B., Spolarics Z., Antonioli L., Cseri K., Erdélyi K., et al. Extracellular ATP protects against sepsis through macrophage P2X7 purinergic receptors by enhancing intracellular bacterial killing. FASEB J. 2015;29:3626–3637. doi: 10.1096/fj.15-272450.
    1. Ren H., Teng Y., Tan B., Zhang X., Jiang W., Liu M., Du B., Qian M. Toll-like receptor-triggered calcium mobilization protects mice against bacterial infection through extracellular ATP release. Infect. Immun. 2014;82:5076–5085. doi: 10.1128/IAI.02546-14.
    1. Taylor K.A., Wright J.R., Vial C., Evans R.J., Mahaut-Smith M.P. Amplification of human platelet activation by surface pannexin-1 channels. J. Thromb. Haemost. 2014;12:987–998. doi: 10.1111/jth.12566.
    1. Sakaki H., Tsukimoto M., Harada H., Moriyama Y., Kojima S. Autocrine regulation of macrophage activation via exocytosis of ATP and activation of P2Y11 receptor. PLoS ONE. 2013;8:e59778. doi: 10.1371/journal.pone.0059778.
    1. Burnstock G. Purinergic signalling and disorders of the central nervous system. Nat. Rev. Drug Discov. 2008;7:575–590. doi: 10.1038/nrd2605.
    1. Moalem G., Tracey D.J. Immune and inflammatory mechanisms in neuropathic pain. Brain Res. Rev. 2006;51:240–264. doi: 10.1016/j.brainresrev.2005.11.004.
    1. Marchand F., Perretti M., McMahon S.B. Role of the immune system in chronic pain. Nat. Rev. Neurosci. 2005;6:521–532. doi: 10.1038/nrn1700.
    1. Cook S.P., Vulchanova L., Hargreaves K.M., Elde R., McCleskey E.W. Distinct ATP receptors on pain-sensing and stretch-sensing neurons. Nature. 1997;387:505–508. doi: 10.1038/387505a0.
    1. Chessell I.P., Hatcher J.P., Bountra C., Michel A.D., Hughes J.P., Green P., Egerton J., Murfin M., Richardson J., Peck W.L., et al. Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain. Pain. 2005;114:386–396. doi: 10.1016/j.pain.2005.01.002.
    1. Coleman R., Body J.J., Aapro M., Hadji P., Herrstedt J., Group E.G.W. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann. Oncol. 2014;25(Suppl. 3):iii124–iii137. doi: 10.1093/annonc/mdu103.
    1. Sivaramakrishnan V., Bidula S., Campwala H., Katikaneni D., Fountain S.J. Constitutive lysosome exocytosis releases ATP and engages P2Y receptors in human monocytes. Pt 19J. Cell Sci. 2012;125:4567–4575. doi: 10.1242/jcs.107318.
    1. McLeish K.R., Dean W.L., Wellhausen S.R., Stelzer G.T. Role of intracellular calcium in priming of human peripheral blood monocytes by bacterial lipopolysaccharide. Inflammation. 1989;13:681–692. doi: 10.1007/BF00914312.
    1. Gouwy M., Struyf S., Noppen S., Schutyser E., Springael J.Y., Parmentier M., Proost P., Van Damme J. Synergy between coproduced CC and CXC chemokines in monocyte chemotaxis through receptor-mediated events. Mol. Pharmacol. 2008;74:485–495. doi: 10.1124/mol.108.045146.
    1. Badolato R., Johnston J.A., Wang J.M., McVicar D., Xu L.L., Oppenheim J.J., Kelvin D.J. Serum amyloid A induces calcium mobilization and chemotaxis of human monocytes by activating a pertussis toxin-sensitive signaling pathway. J. Immunol. 1995;155:4004–4010.
    1. Hishikawa T., Cheung J.Y., Yelamarty R.V., Knutson D.W. Calcium transients during Fc receptor-mediated and nonspecific phagocytosis by murine peritoneal macrophages. J. Cell Biol. 1991;115:59–66. doi: 10.1083/jcb.115.1.59.
    1. MacIntyre J.P., Pope B.L. The involvement of protein kinase C, calcium, and 5-lipoxygenase in the production of tumor necrosis factor by a cloned interleukin-3 dependent cell line with natural cytotoxic activity. Int. J. Immunopharmacol. 1991;13:175–184. doi: 10.1016/0192-0561(91)90096-P.
    1. Eltzschig H.K., Carmeliet P. Hypoxia and inflammation. N. Engl. J. Med. 2011;364:656–665. doi: 10.1056/NEJMra0910283.
    1. Kuhlicke J., Frick J.S., Morote-Garcia J.C., Rosenberger P., Eltzschig H.K. Hypoxia inducible factor (HIF)-1 coordinates induction of Toll-like receptors TLR2 and TLR6 during hypoxia. PLoS ONE. 2007;2:e1364. doi: 10.1371/journal.pone.0001364.
    1. Eltzschig H.K., Ibla J.C., Furuta G.T., Leonard M.O., Jacobson K.A., Enjyoji K., Robson S.C., Colgan S.P. Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: Role of ectonucleotidases and adenosine A2B receptors. J. Exp. Med. 2003;198:783–796. doi: 10.1084/jem.20030891.
    1. Thompson L.F., Eltzschig H.K., Ibla J.C., Van De Wiele C.J., Resta R., Morote-Garcia J.C., Colgan S.P. Crucial role for ecto-5′-nucleotidase (CD73) in vascular leakage during hypoxia. J. Exp. Med. 2004;200:1395–13405. doi: 10.1084/jem.20040915.
    1. Spaans F., de Vos P., Bakker W.W., van Goor H., Faas M.M. Danger signals from ATP and adenosine in pregnancy and preeclampsia. Hypertension. 2014;63:1154–1160. doi: 10.1161/HYPERTENSIONAHA.114.03240.
    1. Lohman A.W., Isakson B.E. Differentiating connexin hemichannels and pannexin channels in cellular ATP release. FEBS Lett. 2014;588:1379–1388. doi: 10.1016/j.febslet.2014.02.004.
    1. Sosinsky G.E., Boassa D., Dermietzel R., Duffy H.S., Laird D.W., MacVicar B., Naus C.C., Penuela S., Scemes E., Spray D.C., et al. Pannexin channels are not gap junction hemichannels. Channels. 2011;5:193–197. doi: 10.4161/chan.5.3.15765.
    1. Scemes E., Spray D.C., Meda P. Connexins, pannexins, innexins: Novel roles of “hemi-channels”. Pflugers Arch. 2009;457:1207–1226. doi: 10.1007/s00424-008-0591-5.
    1. D’hondt C., Ponsaerts R., De Smedt H., Bultynck G., Himpens B. Pannexins, distant relatives of the connexin family with specific cellular functions? Bioessays. 2009;31:953–974. doi: 10.1002/bies.200800236.
    1. Penuela S., Gehi R., Laird D.W. The biochemistry and function of pannexin channels. Biochim. Biophys. Acta. 2013;1828:15–22. doi: 10.1016/j.bbamem.2012.01.017.
    1. Baroja-Mazo A., Barberà-Cremades M., Pelegrín P. The participation of plasma membrane hemichannels to purinergic signaling. Biochim. Biophys. Acta. 2013;1828:79–93. doi: 10.1016/j.bbamem.2012.01.002.
    1. Kang J., Kang N., Lovatt D., Torres A., Zhao Z., Lin J., Nedergaard M. Connexin 43 hemichannels are permeable to ATP. J. Neurosci. 2008;28:4702–4711. doi: 10.1523/JNEUROSCI.5048-07.2008.
    1. Bao L., Locovei S., Dahl G. Pannexin membrane channels are mechanosensitive conduits for ATP. FEBS Lett. 2004;572:65–68. doi: 10.1016/j.febslet.2004.07.009.
    1. Wang N., De Bock M., Decrock E., Bol M., Gadicherla A., Vinken M., Rogiers V., Bukauskas F.F., Bultynck G., Leybaert L. Paracrine signaling through plasma membrane hemichannels. Biochim. Biophys. Acta. 2013;1828:35–50. doi: 10.1016/j.bbamem.2012.07.002.
    1. Tran Van Nhieu G., Clair C., Bruzzone R., Mesnil M., Sansonetti P., Combettes L. Connexin-dependent inter-cellular communication increases invasion and dissemination of Shigella in epithelial cells. Nat. Cell Biol. 2003;5:720–726. doi: 10.1038/ncb1021.
    1. Schock S.C., Leblanc D., Hakim A.M., Thompson C.S. ATP release by way of connexin 36 hemichannels mediates ischemic tolerance in vitro. Biochem. Biophys. Res. Commun. 2008;368:138–144. doi: 10.1016/j.bbrc.2008.01.054.
    1. Retamal M.A., Schalper K.A., Shoji K.F., Orellana J.A., Bennett M.V., Sáez J.C. Possible involvement of different connexin43 domains in plasma membrane permeabilization induced by ischemia-reperfusion. J. Membr. Biol. 2007;218:49–63. doi: 10.1007/s00232-007-9043-y.
    1. Lopez W., Ramachandran J., Alsamarah A., Luo Y., Harris A.L., Contreras J.E. Mechanism of gating by calcium in connexin hemichannels. Proc. Natl. Acad. Sci. USA. 2016;113:E7986–E7995. doi: 10.1073/pnas.1609378113.
    1. Locovei S., Wang J., Dahl G. Activation of pannexin 1 channels by ATP through P2Y receptors and by cytoplasmic calcium. FEBS Lett. 2006;580:239–244. doi: 10.1016/j.febslet.2005.12.004.
    1. Kar R., Batra N., Riquelme M.A., Jiang J.X. Biological role of connexin intercellular channels and hemichannels. Arch. Biochem. Biophys. 2012;524:2–15. doi: 10.1016/j.abb.2012.03.008.
    1. Willecke K., Eiberger J., Degen J., Eckardt D., Romualdi A., Güldenagel M., Deutsch U., Söhl G. Structural and functional diversity of connexin genes in the mouse and human genome. Biol. Chem. 2002;383:725–737. doi: 10.1515/BC.2002.076.
    1. Dourado M., Wong E., Hackos D.H. Pannexin-1 is blocked by its C-terminus through a delocalized non-specific interaction surface. PLoS ONE. 2014;9:e99596. doi: 10.1371/journal.pone.0099596.
    1. Wang N., De Bock M., Decrock E., Bol M., Gadicherla A., Bultynck G., Leybaert L. Connexin targeting peptides as inhibitors of voltage- and intracellular Ca2+-triggered Cx43 hemichannel opening. Neuropharmacology. 2013;75:506–516. doi: 10.1016/j.neuropharm.2013.08.021.
    1. Iyyathurai J., Wang N., D’hondt C., Jiang J.X., Leybaert L., Bultynck G. The SH3-binding domain of Cx43 participates in loop/tail interactions critical for Cx43-hemichannel activity. Cell. Mol. Life Sci. 2017 doi: 10.1007/s00018-017-2722-7.
    1. Leybaert L., Lampe P.D., Dhein S., Kwak B.R., Ferdinandy P., Beyer E.C., Laird D.W., Naus C.C., Green C.R., Schulz R. Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications. Pharmacol. Rev. 2017;69:396–478. doi: 10.1124/pr.115.012062.
    1. Solan J.L., Lampe P.D. Key connexin 43 phosphorylation events regulate the gap junction life cycle. J. Membr. Biol. 2007;217:35–41. doi: 10.1007/s00232-007-9035-y.
    1. Solan J.L., Lampe P.D. Connexin43 phosphorylation: Structural changes and biological effects. Biochem. J. 2009;419:261–272. doi: 10.1042/BJ20082319.
    1. Bao X., Reuss L., Altenberg G.A. Regulation of purified and reconstituted connexin 43 hemichannels by protein kinase C-mediated phosphorylation of Serine 368. J. Biol. Chem. 2004;279:20058–20066. doi: 10.1074/jbc.M311137200.
    1. García I.E., Sánchez H.A., Martínez A.D., Retamal M.A. Redox-mediated regulation of connexin proteins; focus on nitric oxide. Biochim. Biophys. Acta. 2018;1860:91–95. doi: 10.1016/j.bbamem.2017.10.006.
    1. Retamal M.A., Cortés C.J., Reuss L., Bennett M.V., Sáez J.C. S-nitrosylation and permeation through connexin 43 hemichannels in astrocytes: Induction by oxidant stress and reversal by reducing agents. Proc. Natl. Acad. Sci. USA. 2006;103:4475–4480. doi: 10.1073/pnas.0511118103.
    1. Wang N., De Vuyst E., Ponsaerts R., Boengler K., Palacios-Prado N., Wauman J., Lai C.P., De Bock M., Decrock E., Bol M., Vinken M., et al. Selective inhibition of Cx43 hemichannels by Gap19 and its impact on myocardial ischemia/reperfusion injury. Basic Res. Cardiol. 2013;108:309. doi: 10.1007/s00395-012-0309-x.
    1. Eltzschig H.K., Eckle T., Mager A., Küper N., Karcher C., Weissmüller T., Boengler K., Schulz R., Robson S.C., Colgan S.P. ATP release from activated neutrophils occurs via connexin 43 and modulates adenosine-dependent endothelial cell function. Circ. Res. 2006;99:1100–1108. doi: 10.1161/01.RES.0000250174.31269.70.
    1. Robertson J., Lang S., Lambert P.A., Martin P.E. Peptidoglycan derived from Staphylococcus epidermidis induces Connexin43 hemichannel activity with consequences on the innate immune response in endothelial cells. Biochem. J. 2010;432:133–143. doi: 10.1042/BJ20091753.
    1. Rhett J.M., Fann S.A., Yost M.J. Purinergic signaling in early inflammatory events of the foreign body response: Modulating extracellular ATP as an enabling technology for engineered implants and tissues. Tissue Eng. Part B Rev. 2014;20:392–402. doi: 10.1089/ten.teb.2013.0554.
    1. Burnstock G. Dual control of vascular tone and remodelling by ATP released from nerves and endothelial cells. Pharmacol. Rep. 2008;60:12–20.
    1. Ferrari D., Vitiello L., Idzko M., la Sala A. Purinergic signaling in atherosclerosis. Trends Mol. Med. 2015;21:184–192. doi: 10.1016/j.molmed.2014.12.008.
    1. Yuan D., Wang Q., Wu D., Yu M., Zhang S., Li L., Tao L., Harris A.L. Monocyte-endothelial adhesion is modulated by Cx43-stimulated ATP release from monocytes. Biochem. Biophys. Res. Commun. 2012;420:536–541. doi: 10.1016/j.bbrc.2012.03.027.
    1. Tabas I., Lichtman A.H. Monocyte-Macrophages and T Cells in Atherosclerosis. Immunity. 2017;47:621–634. doi: 10.1016/j.immuni.2017.09.008.
    1. Wong C.W., Christen T., Roth I., Chadjichristos C.E., Derouette J.P., Foglia B.F., Chanson M., Goodenough D.A., Kwak B.R. Connexin37 protects against atherosclerosis by regulating monocyte adhesion. Nat. Med. 2006;12:950–954. doi: 10.1038/nm1441.
    1. Faigle M., Seessle J., Zug S., El Kasmi K.C., Eltzschig H.K. ATP release from vascular endothelia occurs across Cx43 hemichannels and is attenuated during hypoxia. PLoS ONE. 2008;3:e2801. doi: 10.1371/journal.pone.0002801.
    1. Chekeni F.B., Elliott M.R., Sandilos J.K., Walk S.F., Kinchen J.M., Lazarowski E.R., Armstrong A.J., Penuela S., Laird D.W., Salvesen G.S., et al. Pannexin 1 channels mediate ‘find-me’ signal release and membrane permeability during apoptosis. Nature. 2010;467:863–867. doi: 10.1038/nature09413.
    1. Sandilos J.K., Chiu Y.H., Chekeni F.B., Armstrong A.J., Walk S.F., Ravichandran K.S., Bayliss D.A. Pannexin 1, an ATP release channel, is activated by caspase cleavage of its pore-associated C-terminal autoinhibitory region. J. Biol. Chem. 2012;287:11303–11311. doi: 10.1074/jbc.M111.323378.
    1. Chiu Y.H., Jin X., Medina C.B., Leonhardt S.A., Kiessling V., Bennett B.C., Shu S., Tamm L.K., Yeager M., Ravichandran K.S., et al. A quantized mechanism for activation of pannexin channels. Nat. Commun. 2017;8:14324. doi: 10.1038/ncomms14324.
    1. Silverman W.R., de Rivero Vaccari J.P., Locovei S., Qiu F., Carlsson S.K., Scemes E., Keane R.W., Dahl G. The pannexin 1 channel activates the inflammasome in neurons and astrocytes. J. Biol. Chem. 2009;284:18143–18151. doi: 10.1074/jbc.M109.004804.
    1. Gulbransen B.D., Bashashati M., Hirota S.A., Gui X., Roberts J.A., MacDonald J.A., Muruve D.A., McKay D.M., Beck P.L., Mawe G.M., et al. Activation of neuronal P2X7 receptor-pannexin-1 mediates death of enteric neurons during colitis. Nat. Med. 2012;18:600–604. doi: 10.1038/nm.2679.
    1. Pelegrin P., Surprenant A. The P2X(7) receptor-pannexin connection to dye uptake and IL-1β release. Purinergic Signal. 2009;5:129–137. doi: 10.1007/s11302-009-9141-7.
    1. Iglesias R., Locovei S., Roque A., Alberto A.P., Dahl G., Spray D.C., Scemes E. P2X7 receptor-Pannexin1 complex: Pharmacology and signaling. Am. J. Physiol. Cell Physiol. 2008;295:C752–C760. doi: 10.1152/ajpcell.00228.2008.
    1. Gödecke S., Roderigo C., Rose C.R., Rauch B.H., Gödecke A., Schrader J. Thrombin-induced ATP release from human umbilical vein endothelial cells. Am. J. Physiol. Cell Physiol. 2012;302:C915–C923. doi: 10.1152/ajpcell.00283.2010.
    1. Pinheiro A.R., Paramos-de-Carvalho D., Certal M., Costa M.A., Costa C., Magalhães-Cardoso M.T., Ferreirinha F., Sévigny J., Correia-de-Sá P. Histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to Ca2+ mobilization and cell proliferation. J. Biol. Chem. 2013;288:27571–27583. doi: 10.1074/jbc.M113.460865.
    1. Pinheiro A.R., Paramos-de-Carvalho D., Certal M., Costa C., Magalhães-Cardoso M.T., Ferreirinha F., Costa M.A., Correia-de-Sá P. Bradykinin-induced Ca2+ signaling in human subcutaneous fibroblasts involves ATP release via hemichannels leading to P2Y12 receptors activation. Cell Commun. Signal. 2013;11:70. doi: 10.1186/1478-811X-11-70.
    1. Retamal M.A. Connexin and Pannexin hemichannels are regulated by redox potential. Front. Physiol. 2014;5:80. doi: 10.3389/fphys.2014.00080.
    1. Boyce A.K.J., Swayne L.A. P2X7 receptor cross-talk regulates ATP-induced pannexin 1 internalization. Biochem. J. 2017;474:2133–2144. doi: 10.1042/BCJ20170257.
    1. Qiu F., Dahl G. A permeant regulating its permeation pore: Inhibition of pannexin 1 channels by ATP. Am. J. Physiol. Cell Physiol. 2009;296:C250–255. doi: 10.1152/ajpcell.00433.2008.
    1. Whyte-Fagundes P., Zoidl G. Mechanisms of pannexin1 channel gating and regulation. Biochim. Biophys. Acta. 2018;1860:65–71. doi: 10.1016/j.bbamem.2017.07.009.
    1. Poornima V., Vallabhaneni S., Mukhopadhyay M., Bera A.K. Nitric oxide inhibits the pannexin 1 channel through a cGMP-PKG dependent pathway. Nitric Oxide. 2015;47:77–84. doi: 10.1016/j.niox.2015.04.005.
    1. Ayna G., Krysko D.V., Kaczmarek A., Petrovski G., Vandenabeele P., Fésüs L. ATP release from dying autophagic cells and their phagocytosis are crucial for inflammasome activation in macrophages. PLoS ONE. 2012;7:e40069. doi: 10.1371/journal.pone.0040069.
    1. Lauber K., Blumenthal S.G., Waibel M., Wesselborg S. Clearance of apoptotic cells: Getting rid of the corpses. Mol Cell. 2004;14:277–287. doi: 10.1016/S1097-2765(04)00237-0.
    1. Qu Y., Misaghi S., Newton K., Gilmour L.L., Louie S., Cupp J.E., Dubyak G.R., Hackos D., Dixit V.M. Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation. J. Immunol. 2011;186:6553–6561. doi: 10.4049/jimmunol.1100478.
    1. Bao Y., Chen Y., Ledderose C., Li L., Junger W.G. Pannexin 1 channels link chemoattractant receptor signaling to local excitation and global inhibition responses at the front and back of polarized neutrophils. J. Biol. Chem. 2013;288:22650–22657. doi: 10.1074/jbc.M113.476283.
    1. Chen Y., Yao Y., Sumi Y., Li A., To U.K., Elkhal A., Inoue Y., Woehrle T., Zhang Q., Hauser C., et al. Purinergic signaling: A fundamental mechanism in neutrophil activation. Sci. Signal. 2010;3:ra45. doi: 10.1126/scisignal.2000549.
    1. Chen Y., Corriden R., Inoue Y., Yip L., Hashiguchi N., Zinkernagel A., Nizet V., Insel P.A., Junger W.G. ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors. Science. 2006;314:1792–1795. doi: 10.1126/science.1132559.
    1. Riteau N., Baron L., Villeret B., Guillou N., Savigny F., Ryffel B., Rassendren F., Le Bert M., Gombault A., Couillin I. ATP release and purinergic signaling: A common pathway for particle-mediated inflammasome activation. Cell Death Dis. 2012;3:e403. doi: 10.1038/cddis.2012.144.
    1. Pelegrin P., Surprenant A. Pannexin-1 mediates large pore formation and interleukin-1β release by the ATP-gated P2X7 receptor. EMBO J. 2006;25:5071–5082. doi: 10.1038/sj.emboj.7601378.
    1. Gombault A., Baron L., Couillin I. ATP release and purinergic signaling in NLRP3 inflammasome activation. Front. Immunol. 2012;3:414. doi: 10.3389/fimmu.2012.00414.
    1. Connors B.W. Tales of a dirty drug: Carbenoxolone, gap junctions, and seizures. Epilepsy Curr. 2012;12:66–68. doi: 10.5698/1535-7511-12.2.66.
    1. Yan J., Li S. The role of the liver in sepsis. Int. Rev. Immunol. 2014;33:498–510. doi: 10.3109/08830185.2014.889129.
    1. Savio L.E.B., de Andrade Mello P., Figliuolo V.R., de Avelar Almeida T.F., Santana P.T., Oliveira S.D.S., Silva C.L.M., Feldbrügge L., Csizmadia E., Minshall R.D., et al. CD39 limits P2X7 receptor inflammatory signaling and attenuates sepsis-induced liver injury. J. Hepatol. 2017;67:716–726. doi: 10.1016/j.jhep.2017.05.021.
    1. Martinon F., Tschopp J. Inflammatory caspases and inflammasomes: Master switches of inflammation. Cell Death Differ. 2007;14:10–22. doi: 10.1038/sj.cdd.4402038.
    1. Zerr M., Hechler B., Freund M., Magnenat S., Lanois I., Cazenave J.P., Léon C., Gachet C. Major contribution of the P2Y₁receptor in purinergic regulation of TNFα-induced vascular inflammation. Circulation. 2011;123:2404–2413. doi: 10.1161/CIRCULATIONAHA.110.002139.
    1. Riegel A.K., Faigle M., Zug S., Rosenberger P., Robaye B., Boeynaems J.M., Idzko M., Eltzschig H.K. Selective induction of endothelial P2Y6 nucleotide receptor promotes vascular inflammation. Blood. 2011;117:2548–2555. doi: 10.1182/blood-2010-10-313957.
    1. Kronlage M., Song J., Sorokin L., Isfort K., Schwerdtle T., Leipziger J., Robaye B., Conley P.B., Kim H.C., Sargin S., et al. Autocrine purinergic receptor signaling is essential for macrophage chemotaxis. Sci. Signal. 2010;3:ra55. doi: 10.1126/scisignal.2000588.

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