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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

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...

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Autores principales: Kanda, Akira, Kondo, Kenji, Hosaka, Naoki, Kobayashi, Yoshiki, Bui, Dan Van, Yun, Yasutaka, Suzuki, Kensuke, Sawada, Shunsuke, Asako, Mikiya, Nakamura, Akihiko, Tomoda, Koichi, Sakata, Yoshiko, Tsuta, Koji, Dombrowicz, David, Kawauchi, Hideyuki, Fujieda, Shigeharu, Iwai, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409781/
https://www.ncbi.nlm.nih.gov/pubmed/30764556
http://dx.doi.org/10.3390/medsci7020022
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author Kanda, Akira
Kondo, Kenji
Hosaka, Naoki
Kobayashi, Yoshiki
Bui, Dan Van
Yun, Yasutaka
Suzuki, Kensuke
Sawada, Shunsuke
Asako, Mikiya
Nakamura, Akihiko
Tomoda, Koichi
Sakata, Yoshiko
Tsuta, Koji
Dombrowicz, David
Kawauchi, Hideyuki
Fujieda, Shigeharu
Iwai, Hiroshi
author_facet Kanda, Akira
Kondo, Kenji
Hosaka, Naoki
Kobayashi, Yoshiki
Bui, Dan Van
Yun, Yasutaka
Suzuki, Kensuke
Sawada, Shunsuke
Asako, Mikiya
Nakamura, Akihiko
Tomoda, Koichi
Sakata, Yoshiko
Tsuta, Koji
Dombrowicz, David
Kawauchi, Hideyuki
Fujieda, Shigeharu
Iwai, Hiroshi
author_sort Kanda, Akira
collection PubMed
description 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.
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spelling pubmed-64097812019-03-25 Eosinophilic Upper Airway Inflammation in a Murine Model Using an Adoptive Transfer System Induces Hyposmia and Epithelial Layer Injury with Convex Lesions Kanda, Akira Kondo, Kenji Hosaka, Naoki Kobayashi, Yoshiki Bui, Dan Van Yun, Yasutaka Suzuki, Kensuke Sawada, Shunsuke Asako, Mikiya Nakamura, Akihiko Tomoda, Koichi Sakata, Yoshiko Tsuta, Koji Dombrowicz, David Kawauchi, Hideyuki Fujieda, Shigeharu Iwai, Hiroshi Med Sci (Basel) Article 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. MDPI 2019-02-05 /pmc/articles/PMC6409781/ /pubmed/30764556 http://dx.doi.org/10.3390/medsci7020022 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kanda, Akira
Kondo, Kenji
Hosaka, Naoki
Kobayashi, Yoshiki
Bui, Dan Van
Yun, Yasutaka
Suzuki, Kensuke
Sawada, Shunsuke
Asako, Mikiya
Nakamura, Akihiko
Tomoda, Koichi
Sakata, Yoshiko
Tsuta, Koji
Dombrowicz, David
Kawauchi, Hideyuki
Fujieda, Shigeharu
Iwai, Hiroshi
Eosinophilic Upper Airway Inflammation in a Murine Model Using an Adoptive Transfer System Induces Hyposmia and Epithelial Layer Injury with Convex Lesions
title Eosinophilic Upper Airway Inflammation in a Murine Model Using an Adoptive Transfer System Induces Hyposmia and Epithelial Layer Injury with Convex Lesions
title_full Eosinophilic Upper Airway Inflammation in a Murine Model Using an Adoptive Transfer System Induces Hyposmia and Epithelial Layer Injury with Convex Lesions
title_fullStr Eosinophilic Upper Airway Inflammation in a Murine Model Using an Adoptive Transfer System Induces Hyposmia and Epithelial Layer Injury with Convex Lesions
title_full_unstemmed Eosinophilic Upper Airway Inflammation in a Murine Model Using an Adoptive Transfer System Induces Hyposmia and Epithelial Layer Injury with Convex Lesions
title_short Eosinophilic Upper Airway Inflammation in a Murine Model Using an Adoptive Transfer System Induces Hyposmia and Epithelial Layer Injury with Convex Lesions
title_sort eosinophilic upper airway inflammation in a murine model using an adoptive transfer system induces hyposmia and epithelial layer injury with convex lesions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409781/
https://www.ncbi.nlm.nih.gov/pubmed/30764556
http://dx.doi.org/10.3390/medsci7020022
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