αVβ3-Integrin and mitochondria mediate astrocyte response to autoreactive immune cells
2023
Аутори:
Milićević, KatarinaBataveljić, Danijela
Bogdanović Pristov, Jelena
Anđus, Pavle
Nikolić, Ljiljana
Остала ауторства
Kanazir, SelmaSavić, Danijela
Тип документа:
Конференцијски прилог (Објављена верзија)
,
© 2023 by Serbian Neuroscience Society and associates
Метаподаци
Приказ свих података о документуАпстракт:
The astrocytic network maintains homeostasis in the central nervous system (CNS)
through interactions with neighboring cells. In the CNS autoimmune disease, multiple
sclerosis (MS), neuroinflammatory conditions modulate these cell-to-cell interactions.
Our previous work revealed that the immune cells infiltrated into the CNS (CNS-IICs)
of experimental autoimmune encemphalomyelitis (EAE) rat, an animal model of MS,
rapidly alter the activity pattern of astrocytes by activating the glial P2X7 receptor
(P2X7R). In the present study we further defined the mechanisms responsible for
astrocytes’ activation in the presence of CNS-IICs. For this purpose, we used an in
vitro experimental setup and monitored Ca2+ dynamics in Fluo-4-labeled cultured
naïve astrocytes following brief bath application of CNS-IICs isolated from the spinal
cord of the EAE rat. Our data indicate that the astroglial αvβ3-integrin is involved in
the initial contact of astrocytes with CNS-IICs, since blocking αvβ3-integrin reduced
the expected astrocytic Ca2+ response. Furthermore, blocking of mitochondrial
Na+
/Ca2+- and H+
/Ca2+- exchangers in astrocytes promoted an augmentation of the
intracellular Ca2+ increase and a higher ATP release after brief exposure to CNS-IICs,
demonstrating that mitochondria regulate the astrocyte-CNS IICs cell-cell interaction.
Overall, our study expands the understanding of astrocytes’ interaction with
autoreactive immune cells that are present in their local environment in an
autoimmune disease. This offers a new conceptual framework for considering direct
astrocyte–immune cell interaction to design new strategies for therapy development in
the treatment of MS.
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200053 (Универзитет у Београду, Институт за мултидисциплинарна истраживања) (RS-MESTD-inst-2020-200053)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200178 (Универзитет у Београду, Биолошки факултет) (RS-MESTD-inst-2020-200178)
У:
- Kanazir S, Savić D, editors. Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. Belgrade: Serbian Neuroscience Society; 2023. p. 101.