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Analyse du rôle de la NADPH oxydase et du stress oxydant dans les cellules dendritiques

Abstract : Dendritic cells play an important role in the development of immune responses; the numerous functional activities of DC, among them their important phagocytic potential, give to these cells the capacity to activate both innate and acquire immune responses. Many authors have shown that during the development of these processes, oxidative mechanisms have a very important role and consequently must be strictly controlled. In dendritic cells, oxygen radicals production is mainly related to an NADPH Oxidase activity (NOX2), that our laboratory was the first to identify in these cells few years ago. This enzymatic complex has an important function in the production of firstly oxygen superoxide radicals and secondly, various reactive oxygen species (ROS) that are produced like hydrogen peroxide. During my PhD, I have developed various protocols, which enabled us to analyse ROS production by dendritic cells. The different results allowed me to demonstrate that other proteins belonging to the family of the Red/Ox controlling elements are produced by dendritic cells: NOX1 and SOD3. My results showed that these proteins play an important role in ROS formation and control, in complement to what was previously demonstrated for NOX2. I have studied also their intracellular localisation, which permitted a better understanding of their respective role in dendritic cells. It was already shown that, after phagocytosis, pathogen degradation in dendritic cells was partially related to NOX2 activity. The work performed in this thesis let us consider a potential impact of NOX1 derived ROS on the control of the apoptosis of dendritic cells or on signalling pathways at nucleus level. Moreover, superoxyde anion dismutation in hydrogen peroxide (H2O2) could be due to the presence of SOD3 that may be found in endocytic compartments rather than the result of spontaneous reactions most often proposed by authors.
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Submitted on : Wednesday, December 19, 2012 - 3:42:17 PM
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  • HAL Id : tel-00767151, version 1


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Manuel Rangel. Analyse du rôle de la NADPH oxydase et du stress oxydant dans les cellules dendritiques. Sciences agricoles. Université de Grenoble, 2012. Français. ⟨NNT : 2012GRENV003⟩. ⟨tel-00767151⟩



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