Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Department of Pediatrics, Institute of Allergy, Immunology, and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan.
Int Arch Allergy Immunol. 2021;182(12):1143-1154. doi: 10.1159/000517184. Epub 2021 Oct 14.
Asthma animal models provide valuable information about the pathogenesis and the treatment of asthma. An ovalbumin (OVA)/complete Freund's adjuvant (CFA)-sensitized model was developed to induce neutrophil-dominant asthma and to investigate whether fungal immunomodulatory peptide-fve (FIP-fve) could improve asthma features in the OVA/CFA-sensitized model.
We used female BALB/c mice and sensitized them intraperitoneally with OVA/CFA on days 1, 2, and 3. On days 14, 17, 21, 24, and 27, they were challenged with intranasal OVA. The airway hyper-responsiveness (AHR) was detected by BUXCO, inflammatory cells were stained with Liu's stain, the cytokines were detected using ELISA, and the airway inflammation was analyzed with hematoxylin and eosin stain.
According to the results, OVA/CFA sensitization could induce AHR, high levels of IgE, and inflammatory cells especially neutrophils infiltration in the lung and airway inflammation. IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17, IL-25, IL-33, and transforming growth factor-β (TGF-β) increased in the OVA/CFA-sensitized mice. OVA/CFA-sensitized mice treated with FIP-fve not only increased IL-12 and IFN-γ but also decreased IL-4, IL-5, IL-6, IL-8, IL-13, IL-17, IL-25, IL-33, and TGF-β in the bronchoalveolar lavage fluid. Moreover, FIP-fve significantly decreased neutrophil infiltration in the lung.
The OVA/CFA model induced neutrophilic asthma successfully, and FIP-fve improved neutrophil-dominant asthma.
哮喘动物模型为哮喘的发病机制和治疗提供了有价值的信息。本研究建立卵清蛋白（OVA）/完全弗氏佐剂（CFA）致敏模型，以诱导中性粒细胞占主导的哮喘，并探讨真菌免疫调节肽-fve（FIP-fve）是否能改善 OVA/CFA 致敏模型中的哮喘特征。
我们使用雌性 BALB/c 小鼠，用 OVA/CFA 腹腔注射致敏，在第 1、2 和 3 天致敏。在第 14、17、21、24 和 27 天，用鼻内 OVA 对其进行攻击。通过 BUXCO 检测气道高反应性（AHR），用 Liu 染色法对炎症细胞进行染色，ELISA 检测细胞因子，苏木精和伊红染色分析气道炎症。
OVA/CFA 致敏可诱导 AHR、高水平的 IgE 和炎症细胞（特别是中性粒细胞）浸润到肺部和气道炎症。OVA/CFA 致敏小鼠的白细胞介素（IL）-4、IL-5、IL-6、IL-8、IL-10、IL-13、IL-17、IL-25、IL-33 和转化生长因子-β（TGF-β）水平升高。FIP-fve 治疗 OVA/CFA 致敏的小鼠不仅增加了 IL-12 和 IFN-γ，还降低了支气管肺泡灌洗液中的 IL-4、IL-5、IL-6、IL-8、IL-13、IL-17、IL-25、IL-33 和 TGF-β。此外，FIP-fve 还显著减少了肺部的中性粒细胞浸润。
OVA/CFA 模型成功诱导中性粒细胞性哮喘，FIP-fve 改善了中性粒细胞主导的哮喘。
