Contribution of Pannexin1 to Experimental Autoimmune Encephalomyelitis

Sarah E. Lutz, Estibaliz González-Fernández, Juan Carlos Chara Ventura, Alberto Pérez-Samartín, Leonid Tarassishin, Hiromitsu Negoro, Naman K. Patel, Sylvia O. Suadicani, Sunhee C. Lee, Carlos Matute, Eliana Scemes

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Pannexin1 (Panx1) is a plasma membrane channel permeable to relatively large molecules, such as ATP. In the central nervous system (CNS) Panx1 is found in neurons and glia and in the immune system in macrophages and T-cells. We tested the hypothesis that Panx1-mediated ATP release contributes to expression of Experimental Autoimmune Encephalomyelitis (EAE), an animal model for multiple sclerosis, using wild-type (WT) and Panx1 knockout (KO) mice. Panx1 KO mice displayed a delayed onset of clinical signs of EAE and decreased mortality compared to WT mice, but developed as severe symptoms as the surviving WT mice. Spinal cord inflammatory lesions were also reduced in Panx1 KO EAE mice during acute disease. Additionally, pharmacologic inhibition of Panx1 channels with mefloquine (MFQ) reduced severity of acute and chronic EAE when administered before or after onset of clinical signs. ATP release and YoPro uptake were significantly increased in WT mice with EAE as compared to WT non-EAE and reduced in tissues of EAE Panx1 KO mice. Interestingly, we found that the P2X7 receptor was upregulated in the chronic phase of EAE in both WT and Panx1 KO spinal cords. Such increase in receptor expression is likely to counterbalance the decrease in ATP release recorded from Panx1 KO mice and thus contribute to the development of EAE symptoms in these mice. The present study shows that a Panx1 dependent mechanism (ATP release and/or inflammasome activation) contributes to disease progression, and that inhibition of Panx1 using pharmacology or gene disruption delays and attenuates clinical signs of EAE.

Original languageEnglish (US)
Article numbere66657
JournalPLoS One
Volume8
Issue number6
DOIs
StatePublished - Jun 20 2013

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Autoimmune Experimental Encephalomyelitis
encephalitis
Adenosine Triphosphate
mice
Knockout Mice
Purinergic P2X7 Receptors
Inflammasomes
Mefloquine
T-cells
Macrophages
Immune system
Neurology
Cell membranes
Ion Channels
spinal cord
Spinal Cord
signs and symptoms (animals and humans)
Neurons
Animals
Genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lutz, S. E., González-Fernández, E., Ventura, J. C. C., Pérez-Samartín, A., Tarassishin, L., Negoro, H., ... Scemes, E. (2013). Contribution of Pannexin1 to Experimental Autoimmune Encephalomyelitis. PLoS One, 8(6), [e66657]. https://doi.org/10.1371/journal.pone.0066657

Contribution of Pannexin1 to Experimental Autoimmune Encephalomyelitis. / Lutz, Sarah E.; González-Fernández, Estibaliz; Ventura, Juan Carlos Chara; Pérez-Samartín, Alberto; Tarassishin, Leonid; Negoro, Hiromitsu; Patel, Naman K.; Suadicani, Sylvia O.; Lee, Sunhee C.; Matute, Carlos; Scemes, Eliana.

In: PLoS One, Vol. 8, No. 6, e66657, 20.06.2013.

Research output: Contribution to journalArticle

Lutz, SE, González-Fernández, E, Ventura, JCC, Pérez-Samartín, A, Tarassishin, L, Negoro, H, Patel, NK, Suadicani, SO, Lee, SC, Matute, C & Scemes, E 2013, 'Contribution of Pannexin1 to Experimental Autoimmune Encephalomyelitis', PLoS One, vol. 8, no. 6, e66657. https://doi.org/10.1371/journal.pone.0066657
Lutz SE, González-Fernández E, Ventura JCC, Pérez-Samartín A, Tarassishin L, Negoro H et al. Contribution of Pannexin1 to Experimental Autoimmune Encephalomyelitis. PLoS One. 2013 Jun 20;8(6). e66657. https://doi.org/10.1371/journal.pone.0066657
Lutz, Sarah E. ; González-Fernández, Estibaliz ; Ventura, Juan Carlos Chara ; Pérez-Samartín, Alberto ; Tarassishin, Leonid ; Negoro, Hiromitsu ; Patel, Naman K. ; Suadicani, Sylvia O. ; Lee, Sunhee C. ; Matute, Carlos ; Scemes, Eliana. / Contribution of Pannexin1 to Experimental Autoimmune Encephalomyelitis. In: PLoS One. 2013 ; Vol. 8, No. 6.
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