Microglia-related increase in NTPDase1 expression during EAE
2019
Autori:
Laketa, DanijelaJakovljević, Marija
Božić, Iva
Bjelobaba, Ivana
Savić, Danijela
Peković, Sanja
Nedeljković, Nadežda
Lavrnja, Irena
Tip dokumenta:
Konferencijski prilog (Objavljena verzija)
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© 2023 by the German Neuroscience Society
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
Ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase1/CD39) is the main ATP- and ADPdegrading
enzyme in extracellular fluid of the central nervous system. In the hydrolysis cascade
NTPDase1 removes ATP and ADP and produces AMP, which is hydrolysed by ecto-5'-nucleotidase to
adenosine. During neuroinflammation, increased extracellular ATP levels exert proinflammatory effects
at microglia as resident immune cells, while adenosine effects are antiinflammatory. Literature data
indicate involvement of purinergic signaling in experimental autoimmune encephalomyelitis (EAE), while
decreased number of NTPDase1/CD39+ regulatory T-cells was evidenced in multiple sclerosis.
Downregulation of NTPDase1 expression was observed in proinflammatory activation phenotype of
macrophages. However, data on the role of NTPDase1 on glial cells in neuroinflammation are still
scarce. We have shown increase in ATP-, ADP- and AMP-hydrolysis, together with upregulated mRNA
and protein expression of NTPDase1 in lumbar spinal cord, correlated to the disease course during EAE.
In this study we aimed to explore contribution of particular cell subsets to the observed changes in
NTPDase1 expression.
Acute monophasic EAE was induced in female rats of Dark Agouti strain by active immunization with a
mixture of spinal cord homogenate in complete Freund’s adjuvant. Immunized animals were sacrificed at
the onset, peak and end of symptoms, while naïve animals were used as control. Significant increase of
NTPDase1 immunofluorescence in lumbar spinal cord cross-sections was related to prominent infiltrates
at the peak of EAE and increased expression of NTPDase1 among isolated mononuclear cells. Analysis
of triple-labeled Arginase1/NTPDase1/Iba1 and iNOS/NTPDase1/Iba1 immunofluorescent micrographs
showed prevalent contribution of Arginase1+ microglia in comparison to iNOS+ microglia in NTPDase1
immunofluorescence, at the peak of EAE. Further studies are needed to reveal possible association of
NTPDase1 with antiinflammatory phenotype in microglia.
U:
- Proceedings: 13th Göttingen Meeting of the German Neuroscience Society 2019 and 37th Göttingen Neurobiology Conference; 2019 Mar 20-23; Göttingen, Germany. German Neuroscience Society; 2019. T12-5B. (Neuroforum ; Vol. 25; Suppl. 1).