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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2015

Autores

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

Revista

Título: Mediators of Inflammation

Vol. 2015

Páginas: 1-16

ISSN: 0962-9351

Editora: Hindawi

Indexação

ISI Web of Knowledge - 20 Citações

ISI Web of Science

Scopus - 22 Citações

Pubmed / Medline

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

CORDIS: Ciências da Saúde > Ciências Médicas > Medicina > Imunologia

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 16