title: The Pig: A Relevant Model for Evaluating the Neutrophil Serine Protease Activities during Acute Pseudomonas aeruginosa Lung Infection.
abstract: The main features of lung infection and inflammation are a massive recruitment of neutrophils and the subsequent release of neutrophil serine proteases (NSPs). Anti-infectious and/or anti-inflammatory treatments must be tested on a suitable animal model. Mice models do not replicate several aspects of human lung disease. This is particularly true for cystic fibrosis (CF), which has led the scientific community to a search for new animal models. We have shown that mice are not appropriate for characterizing drugs targeting neutrophil-dependent inflammation and that pig neutrophils and their NSPs are similar to their human homologues. We induced acute neutrophilic inflammatory responses in pig lungs using Pseudomonas aeruginosa, an opportunistic respiratory pathogen. Blood samples, nasal swabs and bronchoalveolar lavage fluids (BALFs) were collected at 0, 3, 6 and 24 h post-insfection (p.i.) and biochemical parameters, serum and BAL cytokines, bacterial cultures and neutrophil activity were evaluated. The release of proinflammatory mediators, biochemical and hematological blood parameters, cell recruitment and bronchial reactivity, peaked at 6h p.i.. We also used synthetic substrates specific for human neutrophil proteases to show that the activity of pig NSPs in BALFs increased. These proteases were also detected at the surface of lung neutrophils using anti-human NSP antibodies. Pseudomonas aeruginosa-induced lung infection in pigs results in a neutrophilic response similar to that described for cystic fibrosis and ventilator-associated pneumonia in humans. Altogether, this indicates that the pig is an appropriate model for testing anti-infectious and/or anti-inflammatory drugs to combat adverse proteolytic effects of neutrophil in human lung diseases.
authors.affiliation: Infectiologie et Santé Publique (UMR 1282 ISP), INRA, Université Tours, Nouzilly, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Chevaleyre
authors.affiliation: Plateforme d'Infectiologie expérimentale (UE-1277 PFIE), INRA, Nouzilly, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Riou
authors.affiliation: INSERM, Centre d'Etude des Pathologies Respiratoires, UMR 1100, Tours cedex, France.
authors.forename: Déborah
authors.initials: D
authors.lastname: Bréa
authors.affiliation: Laboratoire Signalisation et Transports Ioniques Membranaires, Université de Poitiers, Centre National de la Recherche Scientifique, Poitiers cedex, France.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Vandebrouck
authors.affiliation: Plateforme d'Infectiologie expérimentale (UE-1277 PFIE), INRA, Nouzilly, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Barc
authors.affiliation: Plateforme d'Infectiologie expérimentale (UE-1277 PFIE), INRA, Nouzilly, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Pezant
authors.affiliation: Infectiologie et Santé Publique (UMR 1282 ISP), INRA, Université Tours, Nouzilly, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Melo
authors.affiliation: Infectiologie et Santé Publique (UMR 1282 ISP), INRA, Université Tours, Nouzilly, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Olivier
authors.affiliation: Plateforme d'Infectiologie expérimentale (UE-1277 PFIE), INRA, Nouzilly, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Delaunay
authors.affiliation: Plateforme d'Infectiologie expérimentale (UE-1277 PFIE), INRA, Nouzilly, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Boulesteix
authors.affiliation: Infectiologie et Santé Publique (UMR 1282 ISP), INRA, Université Tours, Nouzilly, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Berthon
authors.affiliation: Infectiologie et Santé Publique (UMR 1282 ISP), INRA, Université Tours, Nouzilly, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Rossignol
authors.affiliation: Département des Microscopies (Plateau technologique Analyse des systèmes Biologiques), Université François-Rabelais, Tours cedex, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Burlaud Gaillard
authors.affiliation: Laboratoire Signalisation et Transports Ioniques Membranaires, Université de Poitiers, Centre National de la Recherche Scientifique, Poitiers cedex, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Becq
authors.affiliation: INSERM, Centre d'Etude des Pathologies Respiratoires, UMR 1100, Tours cedex, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Gauthier
authors.affiliation: INSERM, Centre d'Etude des Pathologies Respiratoires, UMR 1100, Tours cedex, France.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Si-Tahar
authors.affiliation: BioEpAR, Oniris, Nantes Atlantic National College of Veterinary Medicine, Food Science and Engineering La Chantrerie, Nantes Cedex 3, France.
authors.forename: François
authors.initials: F
authors.lastname: Meurens
authors.affiliation: Infectiologie et Santé Publique (UMR 1282 ISP), INRA, Université Tours, Nouzilly, France.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Berri
authors.affiliation: Infectiologie et Santé Publique (UMR 1282 ISP), INRA, Université Tours, Nouzilly, France.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Caballero-Posadas
authors.affiliation: INSERM, Centre d'Etude des Pathologies Respiratoires, UMR 1100, Tours cedex, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Attucci
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000201:enzymology*; D009666:Nose / Q000276:immunology / Q000382:microbiology; D011552:Pseudomonas Infections / Q000201:enzymology / Q000276:immunology*; D011550:Pseudomonas aeruginosa; D057057:Serine Proteases / Q000378:metabolism*; D013552:Swine
chemical_list: D018925:Chemokines; D016207:Cytokines; D057057:Serine Proteases