Human P2Y11 Expression Level Affects Human P2X7 Receptor-Mediated Cell Death
Adenosine triphosphate (ATP) is known to induce cell death in T lymphocytes at high extracellular concentrations. CD4+ and CD8+ T lymphocytes have a differential response to ATP, which in mice is due to differences in the P2X7 receptor expression levels. By contrast, we observed that the difference...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01159/full |
| _version_ | 1811233630102487040 |
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| author | Karin Dreisig Louise Sund Maja Wallentin Dommer Nikolaj Pagh Kristensen Kim Boddum Rannveig Viste Simon Fredholm Niels Odum Marja Jäättelä Søren Skov Birgitte R. Kornum Birgitte R. Kornum |
| author_facet | Karin Dreisig Louise Sund Maja Wallentin Dommer Nikolaj Pagh Kristensen Kim Boddum Rannveig Viste Simon Fredholm Niels Odum Marja Jäättelä Søren Skov Birgitte R. Kornum Birgitte R. Kornum |
| author_sort | Karin Dreisig |
| collection | DOAJ |
| description | Adenosine triphosphate (ATP) is known to induce cell death in T lymphocytes at high extracellular concentrations. CD4+ and CD8+ T lymphocytes have a differential response to ATP, which in mice is due to differences in the P2X7 receptor expression levels. By contrast, we observed that the difference in human CD4+ and CD8+ T lymphocyte response toward the synthetic ATP-analog BzATP is not explained by a difference in human P2X7 receptor expression. Rather, the BzATP-induced human P2X7 receptor response in naïve and immune-activated lymphocyte subtypes correlated with the expression of another ATP-binding receptor: the human P2Y11 receptor. In a recombinant expression system, the coexpression of the human P2Y11 receptor counteracted BzATP-induced human P2X7 receptor-driven lactate dehydrogenase release (a marker of cell death) and pore formation independent of calcium signaling. A mutated non-signaling human P2Y11 receptor had a similar human P2X7 receptor-inhibitory effect on pore formation, thus demonstrating that the human P2X7 receptor interference was not caused by human P2Y11 receptor signaling. In conclusion, we demonstrate an important species difference in the ATP-mediated cell death between mice and human cells and show that in human T lymphocytes, the expression of the human P2Y11 receptor correlates with human P2X7 receptor-driven cell death following BzATP stimulation. |
| first_indexed | 2024-04-12T11:22:55Z |
| format | Article |
| id | doaj.art-11d770213cdf4559ab041b15f59870d7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T11:22:55Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-11d770213cdf4559ab041b15f59870d72022-12-22T03:35:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-06-01910.3389/fimmu.2018.01159300492Human P2Y11 Expression Level Affects Human P2X7 Receptor-Mediated Cell DeathKarin Dreisig0Louise Sund1Maja Wallentin Dommer2Nikolaj Pagh Kristensen3Kim Boddum4Rannveig Viste5Simon Fredholm6Niels Odum7Marja Jäättelä8Søren Skov9Birgitte R. Kornum10Birgitte R. Kornum11Molecular Sleep Laboratory, Department of Clinical Biochemistry, Rigshospitalet, Glostrup Hospital, Glostrup, DenmarkMolecular Sleep Laboratory, Department of Clinical Biochemistry, Rigshospitalet, Glostrup Hospital, Glostrup, DenmarkMolecular Sleep Laboratory, Department of Clinical Biochemistry, Rigshospitalet, Glostrup Hospital, Glostrup, DenmarkMolecular Sleep Laboratory, Department of Clinical Biochemistry, Rigshospitalet, Glostrup Hospital, Glostrup, DenmarkMolecular Sleep Laboratory, Department of Clinical Biochemistry, Rigshospitalet, Glostrup Hospital, Glostrup, DenmarkNorwegian Centre of Expertise for Neurodevelopmental Disorders and Hypersomnias (NevSom), Oslo University Hospital, Ullevål, NorwayDepartment of Immunology and Microbiology, University of Copenhagen, Copenhagen, DenmarkDepartment of Immunology and Microbiology, University of Copenhagen, Copenhagen, DenmarkCell Death and Metabolism Unit, Center for Autophagy, Recycling and Disease, Danish Cancer Society Research Center, Copenhagen, DenmarkDepartment of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkMolecular Sleep Laboratory, Department of Clinical Biochemistry, Rigshospitalet, Glostrup Hospital, Glostrup, DenmarkDanish Center for Sleep Medicine, Department of Neurophysiology, Rigshospitalet, Glostrup Hospital, Glostrup, DenmarkAdenosine triphosphate (ATP) is known to induce cell death in T lymphocytes at high extracellular concentrations. CD4+ and CD8+ T lymphocytes have a differential response to ATP, which in mice is due to differences in the P2X7 receptor expression levels. By contrast, we observed that the difference in human CD4+ and CD8+ T lymphocyte response toward the synthetic ATP-analog BzATP is not explained by a difference in human P2X7 receptor expression. Rather, the BzATP-induced human P2X7 receptor response in naïve and immune-activated lymphocyte subtypes correlated with the expression of another ATP-binding receptor: the human P2Y11 receptor. In a recombinant expression system, the coexpression of the human P2Y11 receptor counteracted BzATP-induced human P2X7 receptor-driven lactate dehydrogenase release (a marker of cell death) and pore formation independent of calcium signaling. A mutated non-signaling human P2Y11 receptor had a similar human P2X7 receptor-inhibitory effect on pore formation, thus demonstrating that the human P2X7 receptor interference was not caused by human P2Y11 receptor signaling. In conclusion, we demonstrate an important species difference in the ATP-mediated cell death between mice and human cells and show that in human T lymphocytes, the expression of the human P2Y11 receptor correlates with human P2X7 receptor-driven cell death following BzATP stimulation.https://www.frontiersin.org/article/10.3389/fimmu.2018.01159/fullP2RY11P2RX7A740003Fluo-4cyclic adenosine monophosphatepurinergic |
| spellingShingle | Karin Dreisig Louise Sund Maja Wallentin Dommer Nikolaj Pagh Kristensen Kim Boddum Rannveig Viste Simon Fredholm Niels Odum Marja Jäättelä Søren Skov Birgitte R. Kornum Birgitte R. Kornum Human P2Y11 Expression Level Affects Human P2X7 Receptor-Mediated Cell Death Frontiers in Immunology P2RY11 P2RX7 A740003 Fluo-4 cyclic adenosine monophosphate purinergic |
| title | Human P2Y11 Expression Level Affects Human P2X7 Receptor-Mediated Cell Death |
| title_full | Human P2Y11 Expression Level Affects Human P2X7 Receptor-Mediated Cell Death |
| title_fullStr | Human P2Y11 Expression Level Affects Human P2X7 Receptor-Mediated Cell Death |
| title_full_unstemmed | Human P2Y11 Expression Level Affects Human P2X7 Receptor-Mediated Cell Death |
| title_short | Human P2Y11 Expression Level Affects Human P2X7 Receptor-Mediated Cell Death |
| title_sort | human p2y11 expression level affects human p2x7 receptor mediated cell death |
| topic | P2RY11 P2RX7 A740003 Fluo-4 cyclic adenosine monophosphate purinergic |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01159/full |
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