Human P2Y11 expression level affects human P2X7 receptor-mediated cell death
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Human P2Y11 expression level affects human P2X7 receptor-mediated cell death. / Dreisig, Karin; Sund, Louise; Dommer, Maja Wallentin; Kristensen, Nikolaj Pagh; Boddum, Kim; Viste, Rannveig; Fredholm, Simon; Odum, Niels; Jäättelä, Marja; Skov, Søren; Kornum, Birgitte R.
In: Frontiers in Immunology, Vol. 9, No. JUN, 1159, 2018.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Human P2Y11 expression level affects human P2X7 receptor-mediated cell death
AU - Dreisig, Karin
AU - Sund, Louise
AU - Dommer, Maja Wallentin
AU - Kristensen, Nikolaj Pagh
AU - Boddum, Kim
AU - Viste, Rannveig
AU - Fredholm, Simon
AU - Odum, Niels
AU - Jäättelä, Marja
AU - Skov, Søren
AU - Kornum, Birgitte R.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - A740003
KW - Cyclic adenosine monophosphate
KW - Fluo-4
KW - P2RX7
KW - P2RY
KW - Purinergic
KW - YO-PRO-1
U2 - 10.3389/fimmu.2018.01159
DO - 10.3389/fimmu.2018.01159
M3 - Journal article
C2 - 29937766
AN - SCOPUS:85048273544
VL - 9
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - JUN
M1 - 1159
ER -
ID: 201910516