Activation of P2X7 Receptors in Peritoneal and Meningeal Mast Cells Detected by Uptake of Organic Dyes: Possible Purinergic Triggers of Neuroinflammation in Meninges

Dilyara Nurkhametova, Igor Kudryavtsev, Valeriia Guselnikova, Maria Serebryakova, Raisa R. Giniatullina, Sara Wojciechowski, Fatma Tore, Albert Rizvanov, Jari Koistinaho, Tarja Malm, Rashid Giniatullin

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Sammanfattning

Extracellular ATP activates inflammasome and triggers the release of multiple cytokines in various immune cells, a process primarily mediated by P2X7 receptors. However, the expression and functional properties of P2X7 receptors in native mast cells in tissues such as meninges where migraine pain originates from have not been explored. Here we report a novel model of murine cultured meningeal mast cells and using these, as well as easily accessible peritoneal mast cells, studied the mechanisms of ATP-mediated mast cell activation. We show that ATP induced a time and dose-dependent activation of peritoneal mast cells as analysed by the uptake of organic dye YO-PRO1 as well as DAPI. Both YO-PRO1 and DAPI uptake in mast cells was mediated by the P2X7 subtype of ATP receptors as demonstrated by the inhibitory effect of P2X7 antagonist A839977. Consistent with this, significant YO-PRO1 uptake was promoted by the P2X7 agonist BzATP. Extracellular ATP-induced degranulation of native and cultured meningeal mast cells was shown with Toluidine Blue staining. Taken together, these data demonstrate the important contribution of P2X7 receptors to ATP-driven activation of mast cells, suggesting these purinergic mechanisms as potential triggers of neuroinflammation and pain sensitization in migraine.
Originalspråkengelska
TidskriftFrontiers in Cellular Neuroscience
Volym13
ISSN1662-5102
DOI
StatusPublicerad - 13 feb 2019
MoE-publikationstypA1 Tidskriftsartikel-refererad

Vetenskapsgrenar

  • 3112 Neurovetenskaper

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Nurkhametova, Dilyara ; Kudryavtsev, Igor ; Guselnikova, Valeriia ; Serebryakova, Maria ; Giniatullina, Raisa R. ; Wojciechowski, Sara ; Tore, Fatma ; Rizvanov, Albert ; Koistinaho, Jari ; Malm, Tarja ; Giniatullin, Rashid. / Activation of P2X7 Receptors in Peritoneal and Meningeal Mast Cells Detected by Uptake of Organic Dyes: Possible Purinergic Triggers of Neuroinflammation in Meninges. I: Frontiers in Cellular Neuroscience. 2019 ; Vol. 13.
@article{dc554451ef7a4c9992bf049f50548905,
title = "Activation of P2X7 Receptors in Peritoneal and Meningeal Mast Cells Detected by Uptake of Organic Dyes: Possible Purinergic Triggers of Neuroinflammation in Meninges",
abstract = "Extracellular ATP activates inflammasome and triggers the release of multiple cytokines in various immune cells, a process primarily mediated by P2X7 receptors. However, the expression and functional properties of P2X7 receptors in native mast cells in tissues such as meninges where migraine pain originates from have not been explored. Here we report a novel model of murine cultured meningeal mast cells and using these, as well as easily accessible peritoneal mast cells, studied the mechanisms of ATP-mediated mast cell activation. We show that ATP induced a time and dose-dependent activation of peritoneal mast cells as analysed by the uptake of organic dye YO-PRO1 as well as DAPI. Both YO-PRO1 and DAPI uptake in mast cells was mediated by the P2X7 subtype of ATP receptors as demonstrated by the inhibitory effect of P2X7 antagonist A839977. Consistent with this, significant YO-PRO1 uptake was promoted by the P2X7 agonist BzATP. Extracellular ATP-induced degranulation of native and cultured meningeal mast cells was shown with Toluidine Blue staining. Taken together, these data demonstrate the important contribution of P2X7 receptors to ATP-driven activation of mast cells, suggesting these purinergic mechanisms as potential triggers of neuroinflammation and pain sensitization in migraine.",
keywords = "3112 Neurosciences",
author = "Dilyara Nurkhametova and Igor Kudryavtsev and Valeriia Guselnikova and Maria Serebryakova and Giniatullina, {Raisa R.} and Sara Wojciechowski and Fatma Tore and Albert Rizvanov and Jari Koistinaho and Tarja Malm and Rashid Giniatullin",
year = "2019",
month = "2",
day = "13",
doi = "10.3389/fncel.2019.00045",
language = "English",
volume = "13",
journal = "Frontiers in Cellular Neuroscience",
issn = "1662-5102",
publisher = "Frontiers Media",

}

Nurkhametova, D, Kudryavtsev, I, Guselnikova, V, Serebryakova, M, Giniatullina, RR, Wojciechowski, S, Tore, F, Rizvanov, A, Koistinaho, J, Malm, T & Giniatullin, R 2019, 'Activation of P2X7 Receptors in Peritoneal and Meningeal Mast Cells Detected by Uptake of Organic Dyes: Possible Purinergic Triggers of Neuroinflammation in Meninges', Frontiers in Cellular Neuroscience, vol. 13. https://doi.org/10.3389/fncel.2019.00045

Activation of P2X7 Receptors in Peritoneal and Meningeal Mast Cells Detected by Uptake of Organic Dyes: Possible Purinergic Triggers of Neuroinflammation in Meninges. / Nurkhametova, Dilyara; Kudryavtsev, Igor; Guselnikova, Valeriia; Serebryakova, Maria; Giniatullina, Raisa R.; Wojciechowski, Sara; Tore, Fatma; Rizvanov, Albert; Koistinaho, Jari; Malm, Tarja; Giniatullin, Rashid.

I: Frontiers in Cellular Neuroscience, Vol. 13, 13.02.2019.

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

TY - JOUR

T1 - Activation of P2X7 Receptors in Peritoneal and Meningeal Mast Cells Detected by Uptake of Organic Dyes: Possible Purinergic Triggers of Neuroinflammation in Meninges

AU - Nurkhametova, Dilyara

AU - Kudryavtsev, Igor

AU - Guselnikova, Valeriia

AU - Serebryakova, Maria

AU - Giniatullina, Raisa R.

AU - Wojciechowski, Sara

AU - Tore, Fatma

AU - Rizvanov, Albert

AU - Koistinaho, Jari

AU - Malm, Tarja

AU - Giniatullin, Rashid

PY - 2019/2/13

Y1 - 2019/2/13

N2 - Extracellular ATP activates inflammasome and triggers the release of multiple cytokines in various immune cells, a process primarily mediated by P2X7 receptors. However, the expression and functional properties of P2X7 receptors in native mast cells in tissues such as meninges where migraine pain originates from have not been explored. Here we report a novel model of murine cultured meningeal mast cells and using these, as well as easily accessible peritoneal mast cells, studied the mechanisms of ATP-mediated mast cell activation. We show that ATP induced a time and dose-dependent activation of peritoneal mast cells as analysed by the uptake of organic dye YO-PRO1 as well as DAPI. Both YO-PRO1 and DAPI uptake in mast cells was mediated by the P2X7 subtype of ATP receptors as demonstrated by the inhibitory effect of P2X7 antagonist A839977. Consistent with this, significant YO-PRO1 uptake was promoted by the P2X7 agonist BzATP. Extracellular ATP-induced degranulation of native and cultured meningeal mast cells was shown with Toluidine Blue staining. Taken together, these data demonstrate the important contribution of P2X7 receptors to ATP-driven activation of mast cells, suggesting these purinergic mechanisms as potential triggers of neuroinflammation and pain sensitization in migraine.

AB - Extracellular ATP activates inflammasome and triggers the release of multiple cytokines in various immune cells, a process primarily mediated by P2X7 receptors. However, the expression and functional properties of P2X7 receptors in native mast cells in tissues such as meninges where migraine pain originates from have not been explored. Here we report a novel model of murine cultured meningeal mast cells and using these, as well as easily accessible peritoneal mast cells, studied the mechanisms of ATP-mediated mast cell activation. We show that ATP induced a time and dose-dependent activation of peritoneal mast cells as analysed by the uptake of organic dye YO-PRO1 as well as DAPI. Both YO-PRO1 and DAPI uptake in mast cells was mediated by the P2X7 subtype of ATP receptors as demonstrated by the inhibitory effect of P2X7 antagonist A839977. Consistent with this, significant YO-PRO1 uptake was promoted by the P2X7 agonist BzATP. Extracellular ATP-induced degranulation of native and cultured meningeal mast cells was shown with Toluidine Blue staining. Taken together, these data demonstrate the important contribution of P2X7 receptors to ATP-driven activation of mast cells, suggesting these purinergic mechanisms as potential triggers of neuroinflammation and pain sensitization in migraine.

KW - 3112 Neurosciences

U2 - 10.3389/fncel.2019.00045

DO - 10.3389/fncel.2019.00045

M3 - Article

VL - 13

JO - Frontiers in Cellular Neuroscience

JF - Frontiers in Cellular Neuroscience

SN - 1662-5102

ER -