title: Mouse model of hypersensitivity pneumonitis after inhalation exposure to different microbial antigens associated with organic dusts.
abstract: The aim of this study was to reproduce in laboratory conditions hypersensitivity pneumonitis (HP) pathogenesis in a new animal model predictive of the human response, and to select the microbial antigen associated with organic dust that exerts the strongest pathogenic effect on the respiratory organ. To achieve this goal, mice of the strain C57BL/6J prone to fibrosis were exposed for 1 hour daily up to 28 days to the inhalation of aerosols of each of the 5 microbial components of organic dusts whose conjunction with the occurrence of HP has been confirmed by numerous authors: Pantoea agglomerans saline extract (SE), P. agglomerans microvesicle-bound endotoxin, Saccharopolyspora rectivirgula SE, Aspergillus fumigatus SE, saline extract of dust from a grain sample overgrown with S. rectivirgula and Thermoactinomyces vulgaris, and a saline solvent (PBS) was used as a control. Exposure of the animals to organic dust components was conducted using a novel inhalation challenge set. Lung samples were collected from untreated mice and from mice exposed for 7 and 28 days, and examined by digitalized histopathology and biochemistry for the presence of inflammatory changes and fibrosis. P. agglomerans SE appeared to be the sole antigen which evoked a statistically significant fibrosis and a significant increase of hydroxyproline in the lungs of mice exposed for 28 days to this extract, both compared to the mice untreated and to those exposed to the solvent. P. agglomerans SE also evoked the strongest and statistically significant inflammatory response in the lungs of the mice, both after 7 and 28 days of exposure. After 7 days, significant inflammatory changes were also found in mice exposed to A. fumigatus SE, and after 28 days in mice exposed to all antigens. In conclusion, our results allow us to define a useful animal model of HP which can be a supplement for now commonly used bleomycin model. This model should comprise: present set of instruments for inhalation, mice of the line C57BL/6J and the saline extract of P. agglomerans as the antigen. For a better understanding of the presented results, a detailed study covering immunological investigations, focused on the mechanism of antigen action, are needed.
authors: Institute of Rural Health, Lublin, Poland. martalemieszek@gmail.com
authors: Marta
authors: M
authors: Lemieszek
authors: Marco
authors: M
authors: Chilosi
authors: Marcin
authors: M
authors: Golec
authors: Czesława
authors: C
authors: Skórska
authors: Francois
authors: F
authors: Huaux
authors: Yousof
authors: Y
authors: Yakoub
authors: Chiara
authors: C
authors: Pastena
authors: Isabella
authors: I
authors: Daniele
authors: Grażyna
authors: G
authors: Cholewa
authors: Jolanta
authors: J
authors: Sitkowska
authors: Wiesława
authors: W
authors: Lisowska
authors: Jacek
authors: J
authors: Zwoliński
authors: Janusz
authors: J
authors: Milanowski
authors: Barbara
authors: B
authors: Mackiewicz
authors: Anna
authors: A
authors: Góra
authors: Jacek
authors: J
authors: Dutkiewicz
mesh_terms: D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology* / Q000473:pathology; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D000946:Antigens, Fungal / Q000276:immunology*; D004391:Dust / Q000276:immunology*; D005260:Female; D019570:Inhalation Exposure; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000942:Antigens, Bacterial; D000946:Antigens, Fungal; D004391:Dust