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Étude métabolomique de la polarisation des macrophages pulmonaires humains

Abstract : Lung macrophages are essential immune cells for defense against pathogens that colonize the respiratory tract and are also involved in the pathophysiology of inflammatory lung diseases such as asthma. Macrophages can be subject to polarization towards two phenotypes called M1 and M2. The M1 phenotype is induced by Toll-like Receptor agonists and promotes the inflammatory response while the M2 phenotype is induced by the canonical Th2 cytokines IL-4 and IL-13 and mainly performs immunoregulatory functions. This differentiation results in changes in phenotype (expression of membrane proteins, production of cytokines) and cellular functions. Polarization also has an impact on metabolism and the production of intracellular mediators.Our objective was to characterize the metabolomic alterations occurring during the M1/M2 polarization in human lung macrophages. Initially, non-targeted and targeted metabolomic methods by liquid chromatography coupled with high-resolution mass spectrometry and gas chromatography coupled with mass spectrometry were developed. These approaches were then applied to identify altered metabolic pathways during M1/M2 polarization (Krebs cycle, kynurenin and arachidonic acid pathways) and to quantify the mediators involved in regulating the inflammatory response, including oxysterols. This work provides a better understanding of cellular metabolism during the polarization of human lung macrophages.
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Fanta Fall. Étude métabolomique de la polarisation des macrophages pulmonaires humains. Médecine humaine et pathologie. Université Paris-Saclay, 2019. Français. ⟨NNT : 2019SACLV064⟩. ⟨tel-02519099⟩

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