Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes
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2020
Authors
Milicevic, KatarinaBijelic, Dunja
Lazarevic, Milica
Miljkovic, Djordje
Bogdanović Pristov, Jelena
Petkovic, Branka
Andjus, Pavle
Momcilovic, Miljana
Nikolic, Ljiljana
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Instituto de neurobiologia
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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by focal neurodegenerative and demyelinating lesions. A major contributor to the pathogenic process of MS is the complex interaction between astrocytes and the CNS-infiltrating immune cells (CNS-IIC). The aim of our study is to explore how naïve astrocytes respond to the autoreactive immune cells that invade the CNS. For this reason, CNS-IICs were isolated and purified from spinal cords of rats with experimental autoimmune encephalomyelitis. Ca2+ dynamics was monitored in Fluo-4 labeled naïve astrocytes, isolated from spinal cords of wild type rat pups, following brief bath application of CNS-IIC or peripheral immune cells, with different pharmacological agents. CNS-IICs, and not peripheral immune cells, induced robust elevation of intracellular Ca2+ in naïve astrocytes. We demonstrated that this CNS IIC-induced increase in astrocyte Ca2+ does not depend on the metabotropic glut...amate receptors, metabotropic purinergic P2Y1 receptors or TRPA1 channels. Remarkably, further research showed that Ca2+ elevation in astrocytes upon exposure to CNS IICs is due to the activation of ionotropic purinergic P2X7 receptors. Bioluminescence assay showed that immune cell-derived ATP is not a cause of astrocytic P2X7 receptor activation. In fact, we showed that CNS-IICs promoted P2X7 receptor activation and increase in cytosolic Ca2+ in astrocytes by astrocytic hemichannel-dependent ATP release mechanism. Our data suggest that direct contact between astrocytes and CNS IICs induce ATP-dependent Ca2+ changes in astrocytes and points to the new aspect of cell-cell interactions in propagation of neuroinflammatory response in CNS autoimmunity.
Keywords:
immune cell / astrocyte / CNS disease / calcium signalingSource:
Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual. Querétaro, México: Instituto de neurobiologia, 2020, 45-Publisher:
- Querétaro, México: Instituto de neurobiologia
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- kategorija M64
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Institut za multidisciplinarna istraživanjaTY - CONF AU - Milicevic, Katarina AU - Bijelic, Dunja AU - Lazarevic, Milica AU - Miljkovic, Djordje AU - Bogdanović Pristov, Jelena AU - Petkovic, Branka AU - Andjus, Pavle AU - Momcilovic, Miljana AU - Nikolic, Ljiljana PY - 2020 UR - http://rimsi.imsi.bg.ac.rs/handle/123456789/2017 AB - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by focal neurodegenerative and demyelinating lesions. A major contributor to the pathogenic process of MS is the complex interaction between astrocytes and the CNS-infiltrating immune cells (CNS-IIC). The aim of our study is to explore how naïve astrocytes respond to the autoreactive immune cells that invade the CNS. For this reason, CNS-IICs were isolated and purified from spinal cords of rats with experimental autoimmune encephalomyelitis. Ca2+ dynamics was monitored in Fluo-4 labeled naïve astrocytes, isolated from spinal cords of wild type rat pups, following brief bath application of CNS-IIC or peripheral immune cells, with different pharmacological agents. CNS-IICs, and not peripheral immune cells, induced robust elevation of intracellular Ca2+ in naïve astrocytes. We demonstrated that this CNS IIC-induced increase in astrocyte Ca2+ does not depend on the metabotropic glutamate receptors, metabotropic purinergic P2Y1 receptors or TRPA1 channels. Remarkably, further research showed that Ca2+ elevation in astrocytes upon exposure to CNS IICs is due to the activation of ionotropic purinergic P2X7 receptors. Bioluminescence assay showed that immune cell-derived ATP is not a cause of astrocytic P2X7 receptor activation. In fact, we showed that CNS-IICs promoted P2X7 receptor activation and increase in cytosolic Ca2+ in astrocytes by astrocytic hemichannel-dependent ATP release mechanism. Our data suggest that direct contact between astrocytes and CNS IICs induce ATP-dependent Ca2+ changes in astrocytes and points to the new aspect of cell-cell interactions in propagation of neuroinflammatory response in CNS autoimmunity. PB - Querétaro, México: Instituto de neurobiologia C3 - Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual. Querétaro, México: Instituto de neurobiologia T1 - Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes SP - 45 UR - https://hdl.handle.net/21.15107/rcub_rimsi_2017 ER -
@conference{ author = "Milicevic, Katarina and Bijelic, Dunja and Lazarevic, Milica and Miljkovic, Djordje and Bogdanović Pristov, Jelena and Petkovic, Branka and Andjus, Pavle and Momcilovic, Miljana and Nikolic, Ljiljana", year = "2020", abstract = "Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by focal neurodegenerative and demyelinating lesions. A major contributor to the pathogenic process of MS is the complex interaction between astrocytes and the CNS-infiltrating immune cells (CNS-IIC). The aim of our study is to explore how naïve astrocytes respond to the autoreactive immune cells that invade the CNS. For this reason, CNS-IICs were isolated and purified from spinal cords of rats with experimental autoimmune encephalomyelitis. Ca2+ dynamics was monitored in Fluo-4 labeled naïve astrocytes, isolated from spinal cords of wild type rat pups, following brief bath application of CNS-IIC or peripheral immune cells, with different pharmacological agents. CNS-IICs, and not peripheral immune cells, induced robust elevation of intracellular Ca2+ in naïve astrocytes. We demonstrated that this CNS IIC-induced increase in astrocyte Ca2+ does not depend on the metabotropic glutamate receptors, metabotropic purinergic P2Y1 receptors or TRPA1 channels. Remarkably, further research showed that Ca2+ elevation in astrocytes upon exposure to CNS IICs is due to the activation of ionotropic purinergic P2X7 receptors. Bioluminescence assay showed that immune cell-derived ATP is not a cause of astrocytic P2X7 receptor activation. In fact, we showed that CNS-IICs promoted P2X7 receptor activation and increase in cytosolic Ca2+ in astrocytes by astrocytic hemichannel-dependent ATP release mechanism. Our data suggest that direct contact between astrocytes and CNS IICs induce ATP-dependent Ca2+ changes in astrocytes and points to the new aspect of cell-cell interactions in propagation of neuroinflammatory response in CNS autoimmunity.", publisher = "Querétaro, México: Instituto de neurobiologia", journal = "Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual. Querétaro, México: Instituto de neurobiologia", title = "Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes", pages = "45", url = "https://hdl.handle.net/21.15107/rcub_rimsi_2017" }
Milicevic, K., Bijelic, D., Lazarevic, M., Miljkovic, D., Bogdanović Pristov, J., Petkovic, B., Andjus, P., Momcilovic, M.,& Nikolic, L.. (2020). Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes. in Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual. Querétaro, México: Instituto de neurobiologia Querétaro, México: Instituto de neurobiologia., 45. https://hdl.handle.net/21.15107/rcub_rimsi_2017
Milicevic K, Bijelic D, Lazarevic M, Miljkovic D, Bogdanović Pristov J, Petkovic B, Andjus P, Momcilovic M, Nikolic L. Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes. in Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual. Querétaro, México: Instituto de neurobiologia. 2020;:45. https://hdl.handle.net/21.15107/rcub_rimsi_2017 .
Milicevic, Katarina, Bijelic, Dunja, Lazarevic, Milica, Miljkovic, Djordje, Bogdanović Pristov, Jelena, Petkovic, Branka, Andjus, Pavle, Momcilovic, Miljana, Nikolic, Ljiljana, "Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes" in Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual. Querétaro, México: Instituto de neurobiologia (2020):45, https://hdl.handle.net/21.15107/rcub_rimsi_2017 .