Department of Respiratory Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan,
Inflamm Res. 2013 Oct;62(10):911-7. doi: 10.1007/s00011-013-0651-y. Epub 2013 Aug 13.
Asthma is associated with eosinophilic airway inflammation and characterized by enhanced airway sensitivity. Interleukin (IL)-5 plays an important role in the pathogenesis of asthma. The involvement of IL-5 receptor-mediated cellular signals in the pathogenesis of a mite antigen-induced chronic asthma model was investigated.
In this study, 48 female C57BL/6J (WT) mice and IL-5 receptor-deficient (IL-5RKO) mice were used.
Mite antigen (50 μl) was intranasally administered 13 times to WT and IL-5RKO mice.
Airway hypersensitivity (Mch PC200) and specific antigen exposure tests were performed, and lung tissue, bronchoalveolar lavage fluid (BALF), and blood were collected to investigate the asthma pathology and differences in the local pulmonary levels of cytokines and chemokines.
Airway sensitivity was enhanced and antigen-specific airway resistance was increased in WT mice. In addition, the number of eosinophils and Th2 cytokine levels in the BALF were increased. In contrast, IL-5RKO mice did not acquire the asthma pathology, such as antigen-specific airway resistance and eosinophilic airway inflammation. Mch PC200 was significantly correlated with cysteinyl leukotriene levels in WT mice.
These findings suggested that both IL-5 induced eosinophils and cysteinyl leukotrienes are involved in the pathology of this mite antigen-induced chronic asthma model.
哮喘与嗜酸性气道炎症有关,其特征是气道敏感性增强。白细胞介素(IL)-5 在哮喘发病机制中起重要作用。本研究旨在探讨 IL-5 受体介导的细胞信号在螨抗原诱导的慢性哮喘模型发病机制中的作用。
本研究使用了 48 只雌性 C57BL/6J(WT)小鼠和 IL-5 受体缺陷(IL-5RKO)小鼠。
螨抗原(50 μl)经鼻腔给予 WT 和 IL-5RKO 小鼠 13 次。
进行气道高反应性(Mch PC200)和特异性抗原暴露试验,并收集肺组织、支气管肺泡灌洗液(BALF)和血液,以研究哮喘病理学和局部肺组织细胞因子和趋化因子水平的差异。
WT 小鼠气道敏感性增强,抗原特异性气道阻力增加,BALF 中嗜酸性粒细胞和 Th2 细胞因子水平升高。相比之下,IL-5RKO 小鼠未出现哮喘病理学改变,如抗原特异性气道阻力和嗜酸性气道炎症。Mch PC200 与 WT 小鼠中半胱氨酰白三烯水平显著相关。
这些发现表明,IL-5 诱导的嗜酸性粒细胞和半胱氨酰白三烯均参与了该螨抗原诱导的慢性哮喘模型的病理学过程。