Laboratory of Molecular Biology, Shanghai Research Institute of Acupuncture and Meridian, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, P.R. China.
Deparment of Acupuncture and Moxibustion, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China.
Immun Inflamm Dis. 2024 Mar;12(3):e1225. doi: 10.1002/iid3.1225.
The dosage of ovalbumin (OVA) during the sensitization stage is considered a crucial factor in the development of airway hyperresponsiveness (AHR). However, the inconsistent dosages of sensitizing OVA used in current studies and the lack of research on their impact on AHR are notable limitations.
We examined the impact of increasing sensitizing doses of OVA in a murine asthma model, which entailed initial sensitization with OVA followed by repeated exposure to OVA aerosols. BALB/c mice were primed with doses of OVA (0, 10, 20, 50, and 100 μg) plus 1 mg Alum on Days 0 and 7, and were challenged with OVA aerosols (10 mg/mL for 30 min) between Days 14 and 17. Antigen-induced AHR to methacholine (MCh), as well as histological changes, eosinophilic infiltration, and epithelial injury were assessed.
The result indicated that there are striking OVA dose-related differences in antigen-induced AHR to MCh. The most intense antigen-induced AHR to MCh was observed with sensitization at 50 μg, while weaker responses were seen at 10, 20, and 100 μg. Meanwhile, there was a significant increase in eosinophil count with sensitization at 50 μg. The changes of AHR were correlated with total cells count, lymphocytes count, eosinophils count, and basophils count in bronchoalveolar lavage fluid; however, it did not correlate with histological changes such as cellular infiltration into bronchovascular bundles and goblet cell hyperplasia of the bronchial epithelium.
Overall, this study demonstrated that sensitization with 50 μg of OVA resulted in the most significant AHR compared to other dosages. These findings may offer valuable insights for future research on mouse asthma modeling protocols.
在致敏阶段卵清蛋白（OVA）的剂量被认为是气道高反应性（AHR）发展的关键因素。然而，目前研究中致敏用 OVA 的剂量不一致，以及缺乏对其对 AHR 影响的研究是显著的局限性。
我们在一个小鼠哮喘模型中研究了增加致敏剂量 OVA 的影响，该模型包括用 OVA 初始致敏，然后反复暴露于 OVA 气溶胶。BALB/c 小鼠在第 0 天和第 7 天用 OVA（0、10、20、50 和 100μg）加 1mg 明矾进行致敏，在第 14 天至第 17 天用 OVA 气溶胶（10mg/mL 持续 30 分钟）进行挑战。评估了抗原诱导的对乙酰甲胆碱（MCh）的 AHR 以及组织学变化、嗜酸性粒细胞浸润和上皮损伤。
结果表明，抗原诱导的对 MCh 的 AHR 与 OVA 剂量存在显著的相关性差异。用 50μg 进行致敏时观察到最强的抗原诱导的对 MCh 的 AHR，而用 10、20 和 100μg 进行致敏时则较弱。同时，用 50μg 进行致敏时嗜酸性粒细胞计数显著增加。AHR 的变化与支气管肺泡灌洗液中的总细胞计数、淋巴细胞计数、嗜酸性粒细胞计数和嗜碱性粒细胞计数相关；然而，它与支气管血管束细胞浸润和支气管上皮杯状细胞增生等组织学变化无关。
总体而言，这项研究表明，与其他剂量相比，用 50μg 的 OVA 致敏导致最显著的 AHR。这些发现可能为未来的小鼠哮喘建模方案研究提供有价值的见解。
