Investigação das ectonucleotidases na diferenciação de macrófagos e na ativação de plaquetas : o papel da homocisteína

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

2010

RESUMO

Extracellular nucleotides modulate a variety of biological actions via purinergic receptor activation. These effects are modulated by ectonucleotidases, such as ENTPDases and ecto-5´- NT/CD73, which hydrolyze ATP to adenosine in the extracellular milieu. In the cells of the immune system, the ATP can act as danger signaling whereas adenosine, the ATP breakdown product, serves as a negative feedback mechanism to limit inflammation. Already, in the vasculare system, the ADP is a physiological agonist involved in normal hemostasis and thrombosis. Since, macrophages are key to inflammatory process, that depending on the microenvironmental stimulation exhibit proinflammatory/ defense (classical/M1) and antiinflammatory/reparatory (alternative/M2) phenotype. The objective of this study was investigate the activity and expression of the ectonuclotidases in differential macrophage phenotype and evaluate the homocysteine (Hcy) effects on theses enzymes in macrophages and platelets. . The analysis of differential macrophages in phenotype proinflamatory/ M1 and antiinflamatory/M2 showed the same expression to P1 and P2 purinoreceptors. However, change profile of the ectonucleotidases as E-NTPDase1, E-NTPDase3 and ecto-5¿- nucleotidase enzymes in macrophages during phenotypic differentiation were found, suggesting that macrophages must alter the purinergic cascade during macrophages differentiation phenotypic. In the pro-inflamatory/M1 phenotype the ATP hydrolysis decreased, suggesting ATP accumulation. On the other hand, the antiinflamatory/M2 phenotype the enzymes lead to a progressive decrease in nucleotides (ATP) concentrations and an increase the adenosine availability. Already, the macrophages exposed to Hcy present a polarized pro-inflammatory profile (M1) and our findings suggest the involvement of the E-NTPDase3 and ecto-5¿-nucleotidase in the inflammatory complications associates to homocysteine. In the Platelets, which are fundamental elements to the thrombogenesis process, the homocysteine decreased ADP hydrolysis. This elevation of ADP around of the platelets due inactivating of ectonucleotidase, probably by the indirect action of Hcy, may be contributing to increase thrombotic risk described in individuals with hyperhomocysteinemia. In addition, the animals that received Hcy treatment potentiate platelet aggregation induced by ADP. In conclusion, in the present study the results reinforce purinergic signaling involvement in inflammatory/thrombosis process and point to development of treatments to inflammatory/thrombotic diseases.

ASSUNTO(S)

5 -nucleotidase ecto-5 -nucleotidase homocisteína receptores purinérgicos

ACESSO AO ARTIGO

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