1. Comparative proteomics of respiratory exosomes in cystic fibrosis, primary ciliary dyskinesia and asthma
- Author
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Cerina Chhuon, Matthieu Bourderioux, Isabelle Sermet-Gaudelus, Virginie Rollet-Cohen, Sophie Guérin-Pfyffer, Ida Chiara Guerrera, Thao Nguyen-Khoa, Aleksander Edelman, Joanna Lipecka, Alain Schmitt, Myriam Mesbahi, Vincent Jung, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), CIC Cochin Pasteur (CIC 1417), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe hospitalier Broca-Université Paris Descartes - Paris 5 (UPD5)-Hôtel-Dieu-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Plateforme protéomique 3P5 [Institut Cochin] (3P5), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement (LAMBE - UMR 8587), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université d'Évry-Val-d'Essonne (UEVE)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5)-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
0301 basic medicine ,Male ,Proteomics ,Adolescent ,Cystic Fibrosis ,Immunoelectron microscopy ,Biophysics ,Respiratory Mucosa ,Exosomes ,Biochemistry ,Exosome ,Cystic fibrosis ,Mass Spectrometry ,03 medical and health sciences ,0302 clinical medicine ,otorhinolaryngologic diseases ,medicine ,Humans ,Child ,Lung ,ComputingMilieux_MISCELLANEOUS ,Primary ciliary dyskinesia ,medicine.diagnostic_test ,business.industry ,Infant ,respiratory system ,medicine.disease ,Asthma ,respiratory tract diseases ,3. Good health ,[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry ,030104 developmental biology ,Bronchoalveolar lavage ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Child, Preschool ,Immunology ,Female ,[PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph] ,business ,Bronchoalveolar Lavage Fluid ,Leukocyte chemotaxis ,Respiratory tract ,Ciliary Motility Disorders - Abstract
Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are pulmonary genetic disorders associated with inflammation and heterogeneous progression of the lung disease. We hypothesized that respiratory exosomes, nanovesicles circulating in the respiratory tract, may be involved in the progression of inflammation-related lung damage. We compared proteomic content of respiratory exosomes isolated from bronchoalveolar lavage fluid in CF and PCD to asthma (A), a condition also associated with inflammation but with less severe lung damage. BALF were obtained from 3 CF, 3 PCD and 6 A patients. Exosomes were isolated from BALF by ultracentrifugations and characterized using immunoelectron microscopy and western-blot. Exosomal protein analysis was performed by high-resolution mass spectrometry using label-free quantification. Exosome enrichment was validated by electron microscopy and immunodetection of CD9, CD63 and ALIX. Mass spectrometry analysis allowed the quantification of 665 proteins, of which 14 were statistically differential according to the disease. PCD and CF exosomes contained higher levels of antioxidant proteins (Superoxide-dismutase, Glutathione peroxidase-3, Peroxiredoxin-5) and proteins involved in leukocyte chemotaxis. All these proteins are known activators of the NF-KappaB pathway. Our results suggest that respiratory exosomes are involved in the pro-inflammatory propagation during the extension of CF or PCD lung diseases. Significance The mechanism of local propagation of lung disease in cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) is not clearly understood. Differential Proteomic profiles of exosomes isolated from BAL from CF, PCD and asthmatic patients suggest that they carry pro-inflammatory proteins that may be involved in the progression of lung damage.
- Published
- 2017
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