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A mouse allergic asthma model induced by shrimp tropomyosin
International Immunopharmacology ( IF 5.6 ) Pub Date : 2020-12-25 , DOI: 10.1016/j.intimp.2020.107289
Lei Fang , Fangchao Zhou , Fan Wu , Ying Yan , Zhenpeng He , Xiaoling Yuan , Xiumei Zhang , Tong Zhang , Duonan Yu

Allergic asthma remains an important worldwide health issue. Animal models are valuable for understanding the pathophysiological mechanisms of asthma and the development of effective therapeutics. This study aims to develop an alternative murine model induced by shrimp tropomyosin (ST) instead of ovalbumin (OVA). To investigate responses to short-term exposure to antigens, mice were sensitized with intraperitoneal injections of ST or ST plus aluminum adjuvant on days 0, 7, 14 followed by an intranasal challenge with ST for seven consecutive days. We reveal that sensitization with ST alone or ST plus aluminum induces significant levels of serum total IgE and ST-specific IgE in mice. Challenge results show that ST causes severe eosinophilic airway inflammation. Histology analysis of the lung tissues demonstrates airway inflammation and mucus hypersecretion within the bronchi in mice exposed to ST. Analysis of the cell composition in bronchoalveolar lavage fluid (BALF) shows a significant increase in eosinophil count in ST alone and ST plus aluminum groups. We also detect increased CD4+ T lymphocytes in lung tissues and production of helper T cell type 2-associated cytokines (IL-4 and IL-5) in BALF. In addition, airway hyperresponsiveness to methacholine in ST alone and ST plus aluminum groups is much higher than that in control groups. For the chronic model, mice were sensitized by ST or ST plus aluminum adjuvant for 3 weeks and challenged with ST for 6 weeks. We find severe structural changes in animals upon prolonged exposure to ST, including goblet cell hyperplasia, collagen deposition, and smooth muscle thickening. In conclusion, ST-induced asthma is a simple murine model for studying pathogenesis of asthma and evaluating new therapeutic drugs.



中文翻译:

虾原肌球蛋白诱导的小鼠过敏性哮喘模型

过敏性哮喘仍然是世界范围内重要的健康问题。动物模型对于理解哮喘的病理生理机制和开发有效的治疗方法非常有价值。这项研究旨在开发由虾原肌球蛋白(ST)代替卵清蛋白(OVA)诱导的另一种小鼠模型。为了研究对短期暴露于抗原的反应,在第0、7、14天通过腹膜内注射ST或ST加铝佐剂使小鼠致敏,然后连续7天鼻内用ST攻击。我们揭示了单独用ST或ST加铝致敏会在小鼠中诱导显着水平的血清总IgE和ST特异性IgE。挑战结果表明,ST引起严重的嗜酸性气道炎症。肺组织的组织学分析表明,暴露于ST的小鼠的气道炎症和支气管内的粘液分泌过多。对支气管肺泡灌洗液(BALF)中细胞组成的分析表明,单独使用ST和ST加铝组的嗜酸性粒细胞计数显着增加。我们还检测到CD4增加肺组织中的T淋巴细胞+和BALF中2型辅助T细胞相关细胞因子(IL-4和IL-5)的产生。此外,仅ST组和ST加铝组的气道对乙酰甲胆碱的反应性高得多。对于慢性模型,用ST或ST加铝佐剂敏化小鼠3周,并用ST攻击6周。我们发现长时间暴露于ST时动物会发生严重的结构变化,包括杯状细胞增生,胶原蛋白沉积和平滑肌增厚。总之,ST诱导的哮喘是研究哮喘的发病机理和评估新治疗药物的简单鼠类模型。

更新日期:2020-12-25
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