Sang Chul Park1, Soo In Kim2,3, Chi Sang Hwang4, Hyung-Ju Cho1,3,5, Joo-Heon Yoon1,3,5,6, Chang-Hoon Kim7,8,9,10. 1. Department of Otorhinolaryngology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea. 2. Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. 3. Korea Mouse Phenotyping Center, Seoul, South Korea. 4. Department of Otorhinolaryngology, Yonsei University Wonju College of Medicine, Wonju, South Korea. 5. The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, South Korea. 6. Global Research Laboratory for Allergic Airway Diseases, Seoul, South Korea. 7. Department of Otorhinolaryngology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea. entman@yuhs.ac. 8. Korea Mouse Phenotyping Center, Seoul, South Korea. entman@yuhs.ac. 9. The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, South Korea. entman@yuhs.ac. 10. Medical Research Center, Yonsei University College of Medicine, Seoul, South Korea. entman@yuhs.ac.
Abstract
PURPOSE: Several murine models have been established to mimic human eosinophilic chronic rhinosinusitis (ECRS). However, in most of these models, ECRS was induced using ovalbumin, which does not cause sinusitis in humans. Thus, we aimed to develop a more clinically relevant murine model of ECRS using multiple airborne allergens. We also investigated the effects of exposure duration of the allergens on ECRS development. METHODS: C57BL/6 mice were intranasally administered multiple airborne allergens (house dust mite, Aspergillus fumigatus, Alternaria alternata, and protease from Staphylococcus aureus) three times weekly for 4, 8, 12, and 16 consecutive weeks. Histopathological changes, the levels of cytokines and chemokines in the nasal lavage fluid, and immune cells of the blood and spleen were analyzed. RESULTS: The mice administered multiple allergens showed significantly increased eosinophil infiltration, epithelial thickening and disruption, and subepithelial collagen deposition from 8 weeks compared to the control group. Goblet cell hyperplasia, polyp-like lesions, and blood eosinophils, as well as the levels of interleukin-5 and eotaxin in the nasal lavage fluid were considerably increased in the ECRS group from 12 weeks compared to those of controls. Instillation of allergens for 16 weeks exacerbated the eosinophil infiltration and eotaxin increase in the nasal lavage fluid. CONCLUSIONS: We successfully established a new murine model of ECRS using more clinically relevant multiple airborne allergens. Prolonged exposure to airborne allergens for 12 weeks or more, corresponding to the definition of human ECRS, strongly induced eosinophil infiltration as well as epithelial remodeling.
PURPOSE: Several murine models have been established to mimic humaneosinophilic chronic rhinosinusitis (ECRS). However, in most of these models, ECRS was induced using ovalbumin, which does not cause sinusitis in humans. Thus, we aimed to develop a more clinically relevant murine model of ECRS using multiple airborne allergens. We also investigated the effects of exposure duration of the allergens on ECRS development. METHODS: C57BL/6 mice were intranasally administered multiple airborne allergens (house dust mite, Aspergillus fumigatus, Alternaria alternata, and protease from Staphylococcus aureus) three times weekly for 4, 8, 12, and 16 consecutive weeks. Histopathological changes, the levels of cytokines and chemokines in the nasal lavage fluid, and immune cells of the blood and spleen were analyzed. RESULTS: The mice administered multiple allergens showed significantly increased eosinophil infiltration, epithelial thickening and disruption, and subepithelial collagen deposition from 8 weeks compared to the control group. Goblet cell hyperplasia, polyp-like lesions, and blood eosinophils, as well as the levels of interleukin-5 and eotaxin in the nasal lavage fluid were considerably increased in the ECRS group from 12 weeks compared to those of controls. Instillation of allergens for 16 weeks exacerbated the eosinophil infiltration and eotaxin increase in the nasal lavage fluid. CONCLUSIONS: We successfully established a new murine model of ECRS using more clinically relevant multiple airborne allergens. Prolonged exposure to airborne allergens for 12 weeks or more, corresponding to the definition of human ECRS, strongly induced eosinophil infiltration as well as epithelial remodeling.
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