Deficits in Endogenous Adenosine Formation by Ecto-5 '-Nucleotidase/CD73 Impair Neuromuscular Transmission and Immune Competence in Experimental Autoimmune Myasthenia Gravis

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Laura Oliveira (Author) ICBAS; Alexandra Correia (Author) ICBAS; Ana Cristina Costa (Author) ICBAS; Sónia Guerra-Gomes (Author) ICBAS; Fátima Ferreirinha (Author) ICBAS; Maria Teresa Magalhães-Cardoso (Author) ICBAS; Manuel Vilanova (Author) ICBAS; Paulo Correia de Sá (Author) ICBAS

Journal

Title: Mediators of Inflammation

Vol. 2015

Pages: 1-16

ISSN: 0962-9351

Publisher: Hindawi

Indexing

ISI Web of Knowledge - 20 Citations

ISI Web of Science

Scopus - 21 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences > Basic medicine

CORDIS: Health sciences > Medical sciences > Medicine > Immunology

Other information

Authenticus ID: P-00A-701

DOI: 10.1155/2015/460610

Abstract (EN): AMP dephosphorylation via ecto-5'-nucleotidase/CD73 is the rate limiting step to generate extracellular adenosine (ADO) from released adenine nucleotides. ADO, via A 2A receptors (A(2A)Rs), is a potent modulator of neuromuscular and immunological responses. The pivotal role of ecto-5'-nucleotidase/CD73, in controlling extracellular ADO formation, prompted us to investigate its role in a rat model of experimental autoimmune myasthenia gravis (EAMG). Results show that CD4+ CD25+ FoxP(3+) regulatory T cells express lower amounts of ecto-5'-nucleotidase/CD73 as compared to controls. Reduction of endogenous ADO formation might explain why proliferation of CD4+ T cells failed upon blocking A(2A) receptors activation with ZM241385 or adenosine deaminase in EAMG animals. Deficits in ADOalso contribute to neuromuscular transmission failure in EAMG rats. Rehabilitation of A(2A)R-mediated immune suppression and facilitation of transmitter release were observed by incubating the cells with the nucleoside precursor, AMP. These findings, together with the characteristic increase in serum adenosine deaminase activity of MG patients, strengthen our hypothesis that the adenosinergic pathway may be dysfunctional in EAMG. Given that endogenous ADO formation is balanced by ecto-5'-nucleotidase/CD73 activity and that A(2A)Rs exert a dual role to restore use-dependent neurocompetence and immune suppression in myasthenics, we hypothesize that stimulation of the two mechanisms may have therapeutic potential in MG.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 16