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Eosinophilic Upper Airway Inflammation in a Murine Model Using an Adoptive Transfer System Induces Hyposmia and Epithelial Layer Injury with Convex Lesions

1
Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, Hirakata 573-1010, Japan
2
Allergy Center, Kansai Medical University, Hirakata 573-1010, Japan
3
Department of Otolaryngology and Head and Neck Surgery, Graduate School of Medicine, the University of Tokyo Hospital, Tokyo, 113-8655, Japan
4
Department of Pathology, Fuchu Hospital, Izumi 594-0076, Japan
5
Nakamura ENT Clinic, Sakai 591-8025, Japan
6
Central Research Laboratory, Kansai Medical University, Hirakata 573-1010, Japan
7
Department of Pathology, Kansai Medical University, Hirakata 573-1010, Japan
8
EGID, Inserm, CHU Lille, Institut Pasteur de Lille, U1011, University of Lille, 59019 Lille, France
9
Department of Otorhinolaryngology, Shimane University Faculty of Medicine, Izumo 693-0021, Japan
10
Department of Otorhinolaryngology Head & Neck Surgery, University of Fukui, Fukui 910-1193, Japan
*
Author to whom correspondence should be addressed.
Equally contributed authors.
Med. Sci. 2019, 7(2), 22; https://doi.org/10.3390/medsci7020022
Received: 18 January 2019 / Revised: 28 January 2019 / Accepted: 30 January 2019 / Published: 5 February 2019
(This article belongs to the Special Issue Chronic Rhinosinusitis and Concomitant Medical Disorders)
Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a refractory upper airway disease, accompanied mainly by eosinophilia and/or asthma. In addition, the disease correlates with a high rate of hyposmia, following a marked infiltration of eosinophils into the inflamed site, the paranasal sinus. Although eosinophils are known to contribute to the development of hyposmia and CRSwNP pathology, the underlying mechanisms remain unclear. This study aimed to investigate whether eosinophilic upper airway inflammation induces hyposmia and CRSwNP in a murine model using an adoptive transfer system. Methods: To induce eosinophilic rhinosinusitis, splenocytes, including a high proportion (over 50%) of activated eosinophils (SPLhEos), were collected from interleukin-5 transgenic mice following double intraperitoneal injections of antigens, such as ovalbumin, house dust mite, or fungus. Activated SPLhEos with corresponding antigens were then transferred into the nasal cavity of recipient mice, which were sensitized and challenged by the corresponding antigen four times per week. Olfactory function, histopathological, and computed tomography (CT) analyses were performed 2 days after the final transfer of eosinophils. Results: Hyposmia was induced significantly in mice that received SPLhEos transfer compared with healthy and allergic mice, but it did not promote morphological alteration of the paranasal sinus. Pathological analysis revealed that epithelial layer injury and metaplasia similar to polyps, with prominent eosinophil infiltration, was induced in recipient tissue. However, there was no nasal polyp development with interstitial edema that was similar to those recognized in human chronic rhinosinusitis. Conclusions: This study supports the previously unsuspected contribution of eosinophils to CRS development in the murine model and suggests that murine-activated eosinophilic splenocytes contribute to the development of hyposmia due to more mucosal inflammation than physical airway obstruction and epithelial layer injury with convex lesions. View Full-Text
Keywords: allergic rhinitis; chronic rhino sinusitis; nasal poly; eosinophil; hyposmia allergic rhinitis; chronic rhino sinusitis; nasal poly; eosinophil; hyposmia
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Kanda, A.; Kondo, K.; Hosaka, N.; Kobayashi, Y.; Bui, D.V.; Yun, Y.; Suzuki, K.; Sawada, S.; Asako, M.; Nakamura, A.; Tomoda, K.; Sakata, Y.; Tsuta, K.; Dombrowicz, D.; Kawauchi, H.; Fujieda, S.; Iwai, H. Eosinophilic Upper Airway Inflammation in a Murine Model Using an Adoptive Transfer System Induces Hyposmia and Epithelial Layer Injury with Convex Lesions. Med. Sci. 2019, 7, 22.

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