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Metabolic adaptation of inflammatory neutrophils in human diseases revealed by retroviral envelope-derived ligands : focus on cystic fibrosis

Abstract : The present study focuses on adaptive metabolic steps adopted by neutrophils during inflammation, particularly during their recruitment into the cystic fibrosis (CF) airways. In CF, we previously described that airway neutrophils are alive and undergo reprogramming, featuring notably the activation of the anabolic mTOR pathway. The present work is based on specific properties of soluble ligands derived from the receptor-binding domains (RBD) of retroviral glycoprotein envelopes, which can be used for the detection of metabolite transporters at the cell surface. First, we validated the use of this new set of markers for the identification and characterization of the metabolic phenotype of CF leukocytes obtained from distinct compartments (blood and sputum). Second, by studying the metabolite transporter expression on blood neutrophils from CF or rheumatoid arthritis patients and control subjects, we distinguished metabolic phenotypes characteristic of specific inflammatory states. Then, we compared metabolite transporter expression between CF blood and airway neutrophils and showed that neutrophils undergo significant metabolic adaptation upon recruitment into the lungs. Finally, we demonstrated that CF airway neutrophils display significant transcriptional modulation and that despite their metabolic reprogramming, they remain functionally competent, thus adding an additional angle of approach to neutrophil studies with regard to inflammation, notably during CF airway disease.
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https://tel.archives-ouvertes.fr/tel-01021456
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Submitted on : Wednesday, July 9, 2014 - 2:22:13 PM
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Julie Laval. Metabolic adaptation of inflammatory neutrophils in human diseases revealed by retroviral envelope-derived ligands : focus on cystic fibrosis. Agricultural sciences. Université Montpellier II - Sciences et Techniques du Languedoc, 2013. English. ⟨NNT : 2013MON20111⟩. ⟨tel-01021456⟩

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