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Effets des particules fines atmosphériques sur la sécrétion des cytokines pro-inflammatoires par les cellules THP-1 et mesures de marqueurs du stress oxydant

Abstract : Particles are concerning constituent of the atmospheric pollution, in particular the PM2,5 fraction (aerodynamic diameter lower than 2,5 µm) which is capable of penetrating into lungs up to alveoli. It can be the cause of inflammation processes leading to respiratory diseases. Studies have shown that alveolar macrophages exposed to PM2,5 secrete inflammatory cytokines. Identification of PM2,5 compounds responsible for observed effects, is not clarified yet. Factors such as the composition in metals and organic compounds, as well as the physical characteristics of particles have all been proposed as being involved in the induction of the inflammatory response. The aim of this thesis is to study in vitro effects of particles on the immune response of macrophages, specifically of the cell line THP-1. The parameters measured are the secretion of inflammatory and oxidative stress markers, in order to give a mechanistic explanation of observed phenomena. It was shown that PM2,5 induce in a significant way the secretion of cytokines IL-1[bêta] and IL-8. Black carbon particles (fine and ultrafine) coated with metals do not (or very slightly induce) a secretion of cytokines superior to that induced by uncoated particles. On the contrary, effect of polycyclic aromatic hydrocarbons (PAHs) adsorbed on particles surface depends on its size. Comparison between the effects of PAHs alone and those adsorbed on particles, showed that ultrafine particles potentiate PAH effects. Particle size appears to be the most determining parameter in the modulation of cytokines secretion. Ultrafine particles, characterized by a strong oxidizing potential, also induce an oxidative stress in vitro. They lead to the formation of a lipid peroxidation product, the HNE which is a mediator of the oxidative stress. However, HNE does not mime the oxidative stress induced by ultrafine particles
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Stéphane Goulaouic. Effets des particules fines atmosphériques sur la sécrétion des cytokines pro-inflammatoires par les cellules THP-1 et mesures de marqueurs du stress oxydant. Toxicologie. Université Paul Verlaine - Metz, 2009. Français. ⟨NNT : 2009METZ018S⟩. ⟨tel-01752636⟩

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