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The role of uric acid and its metabolites on the microbicidal activity of innate immune cells

Grant number: 14/01936-2
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2014
Effective date (End): October 31, 2015
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Flavia Carla Meotti
Grantee:João Pedro Pereira Bonifacio Lopes
Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:11/18106-4 - Oxidation of uric acid by myeloperoxidase in inflammatory processes and the implications for cardiovascular disease, AP.JP


Uric aciishas been considered the main antioxidant in human serum. On the other hand, uric acid has been described to increase oxidative stress damage and to inactivate enzymes that are susceptible to oxidation. The pro-oxidant effect of uric acid causes endothelial dysfunction. High levels of uric acid are related to an increased risk for the development of cardiovascular disease. It can trigger inflammatory response by crystals formation. Our group has investigated the effects of uric acid in the inflammatory environmental and what we have found is that uric acid, at the concentration that is present in plasma can be oxidized by isolated myeloperoxidase and by activated neutrophils. The urate oxidation generates the urate free radical, urate hydroperoxide, 5-hydroxydehydroisourato and alantoin. Because urate is preferential substrate for myeloperoxidase in inflammation, we hypothesized that its oxidized intermediates would increase the microbicidal activity of neutrophils and macrophages. Surprisingly, when incubated with urate, the immune cells lost their ability to kill Pseudomonas aeruginosa. In addition, there was a significant decrease in cytokines release, TNF-± and IL-1², in cells incubated with urate. The reduction in cytokines levels was not due to a reduction on neutrophils viability, as evaluated by flow cytometry. In this context, the aim of this study is to identify the molecular mechanisms in the decrease of microbicidal activity of neutrophils by uric acid or its metabolites.

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