Navegando por Assunto "Adenosine"

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Extracellular nucleotide metabolism in Leishmania : influence of adenosine in the establishment of infection.
(2008) Silva, Eduardo de Almeida Marques da; Oliveira, Jamile Camargos de; Figueiredo, Amanda Braga de; Lima Júnior, Djalma de Souza; Carneiro, Cláudia Martins; Fietto, Juliana Lopes Rangel; Afonso, Luís Carlos Crocco
Leishmaniasis is a parasitic disease with a variety of clinical forms, which are related to the Leishmania species involved. In the murine model, Leishmania amazonensis causes chronic non-healing lesions in Leishmania braziliensis- or Leishmania major-resistant mouse strains. In this study, we investigated the involvement of the pathway of extracellular nucleotide hydrolysis, with special focus on the role of extracellular adenosine, in the establishment of Leishmania infection. Our results show that the more virulent parasitedL. Amazonensisdhydrolyzes higher amounts of ATP, ADP and AMP than the two other species, probably due to the higher expression of membrane NTPDase. Corroborating the idea that increased production of adenosine is important to lesion development and establishment of tissue parasitism, we observed that increased 50-nucleotidase activity in L. braziliensis or addition of adenosine at the moment of infection with this parasite resulted in an increase in lesion size and parasitism as well as a delay in lesion healing. Furthermore, inhibition of adenosine receptor A2B led to decreased lesion size and parasitism. Thus, our results suggest that the conversion of ATP, a molecule with pro-inflammatory activity, into adenosine, which possesses immunomodulatory properties, may contribute to the establishment of infection by Leishmania.
The influence of ecto-nucleotidases on Leishmania amazonensis infection and immune response in C57B/6 mice.
(2010) Testasicca, Miriam Conceição de Souza; Assis, Elisângela Aparecida de; Gomes, Rodrigo Saar; Silva, Eduardo de Almeida Marques da; Melo, Maria Norma; Fietto, Juliana Lopes Rangel; Afonso, Luís Carlos Crocco
Previous results from our laboratory and from the literature have implicated the expression of ectonucleotidases in the establishment of Leishmania infection. In the present study we evaluated the correlation between ecto-nucleotidasic activity and the infectivity of L. amazonensis promastigotes that were kept in culture for short or extended numbers of passages, a condition that is known to decrease parasite infectivity. We also analyzed the immune response associated with the infection by these parasites. As expected, we found that long-term cultured parasites induce the development of smaller lesions than the short-term cultured counterparts. Interestingly, long-term cultured parasites presented reduced ecto-nucleotidasic activity. In addition, cells recovered from animals infected with long-term cultured parasites produced higher amounts of IFN-_ and have smaller parasite load, after 8 weeks of infection. Furthermore, after 1 week of infection, there is increased expression of the chemokine CCL2 mRNA in animals infected with short-term cultured parasites. Finally, infection of peritoneal macrophages by these parasites also shows marked differences. Thus, while short-term cultured parasites are able to infect a greater proportion of macrophages, cells infected by long-term cultured parasites express higher amounts of CXCL10 mRNA, which may activate these cells to kill the parasites. We suggest that the enzymes involved in metabolism of extracellular nucleotides may have an important role in infection by L. amazonensis, by acting directly in its adhesion to target cells and by modulating host cell chemokine production.