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
Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, Hirakata 573-1010, Japan.
Allergy Center, Kansai Medical University, Hirakata 573-1010, Japan.
Med Sci (Basel). 2019 Feb 5;7(2):22. doi: 10.3390/medsci7020022.
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.
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.
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.
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.
伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）是一种难治性上气道疾病，主要伴有嗜酸性粒细胞增多和/或哮喘。此外，该疾病与嗅觉减退发生率高相关，嗜酸性粒细胞显著浸润到炎症部位即鼻窦后会出现嗅觉减退。虽然已知嗜酸性粒细胞会导致嗅觉减退和CRSwNP病理改变，但其潜在机制仍不清楚。本研究旨在使用过继转移系统在小鼠模型中研究嗜酸性上气道炎症是否会诱发嗅觉减退和CRSwNP。
为诱导嗜酸性鼻-鼻窦炎，在腹腔内两次注射抗原（如卵清蛋白、屋尘螨或真菌）后，从白细胞介素-5转基因小鼠中收集脾细胞，其中活化嗜酸性粒细胞比例较高（超过50%）（SPLhEos）。然后将带有相应抗原的活化SPLhEos转移到受体小鼠的鼻腔中，受体小鼠每周接受4次相应抗原的致敏和激发。在最后一次转移嗜酸性粒细胞2天后进行嗅觉功能、组织病理学和计算机断层扫描（CT）分析。
与健康小鼠和过敏小鼠相比，接受SPLhEos转移的小鼠显著出现嗅觉减退，但未促进鼻窦形态改变。病理分析显示，受体组织中诱导出现了类似于息肉的上皮层损伤和化生，伴有显著的嗜酸性粒细胞浸润。然而，没有出现类似于人类慢性鼻-鼻窦炎中所见的伴有间质水肿的鼻息肉形成。
本研究支持了嗜酸性粒细胞在小鼠模型中对CRS发展有此前未被怀疑的作用，并表明小鼠活化的嗜酸性脾细胞由于黏膜炎症多于气道物理阻塞和伴有凸形病变的上皮层损伤，从而导致嗅觉减退的发生。
