Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes
2020
Аутори:
Milićević, KatarinaBijelić, Dunja
Lazarević, Milica
Miljković, Đorđe
Bogdanović Pristov, Jelena
Petković, Branka
Anđus, Pavle
Momčilović, Miljana
Nikolić, Ljiljana
Тип документа:
Конференцијски прилог (Објављена верзија)
,
© 2020 by the Instituto de neurobiologia
Метаподаци
Приказ свих података о документуАпстракт:
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.
Кључне речи:
immune cell; astrocyte; CNS disease; calcium signalingУ:
- Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual. Querétaro, México: Instituto de neurobiologia; 2020. p. 45.