title: Involvement of exosomes in lung inflammation associated with experimental acute pancreatitis.
abstract: A frequent complication of acute pancreatitis is the lung damage associated with the systemic inflammatory response. Although various pro-inflammatory mediators generated at both local and systemic levels have been identified, the pathogenic mechanisms of the disease are still poorly understood. In recent years, exosomes have emerged as a new intercellular communication system able to transfer encapsulated proteins and small RNAs and protect them from degradation. Using an experimental model of taurocholate-induced acute pancreatitis in rats, we aimed to evaluate the role of exosomes in the extent of the systemic inflammatory response. Induction of pancreatitis increased the concentration of circulating exosomes, which showed a different proteomic profile to those obtained from control animals. A series of tracking experiments using PKH26-stained exosomes revealed that circulating exosomes effectively reached the alveolar compartment and were internalized by macrophages. In vitro experiments revealed that exosomes obtained under inflammatory conditions activate and polarize these alveolar macrophages towards a pro-inflammatory phenotype. Interestingly, the proteomic analysis of circulating exosomes during acute pancreatitis suggested a multi-organ origin with a relevant role for the liver as a source of these vesicles. Tracking experiments also revealed that the liver retains the majority of exosomes from the peritoneal cavity. We conclude that exosomes are involved in the lung damage associated with experimental acute pancreatitis and could be relevant mediators in the systemic effects of pancreatitis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors.affiliation: Department of Experimental Pathology, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (IIBB-CSIC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Bonjoch
authors.affiliation: Consejo Superior de Investigaciones Científicas/Universitat Autònoma de Barcelona (CSIC/UAB) Proteomics Facility, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Casas
authors.affiliation: Consejo Superior de Investigaciones Científicas/Universitat Autònoma de Barcelona (CSIC/UAB) Proteomics Facility, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Carrascal
authors.affiliation: Department of Experimental Pathology, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (IIBB-CSIC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. daniel.closa@iibb.csic.es.
authors.forename: Daniel
authors.initials: D
authors.lastname: Closa
mesh_terms: D000818:Animals; D055354:Exosomes / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000473:pathology; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D011014:Pneumonia / Q000209:etiology / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid
chemical_list: D013656:Taurocholic Acid
keywords: alveolar macrophage; exosomes; inflammation; liver; pancreatitis