BackgroundThe 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.MethodsWe 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.ResultsThe 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.ConclusionOverall, 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.

中文翻译：

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增加卵清蛋白致敏剂量对哮喘小鼠气道高反应性的影响

背景致敏阶段卵清蛋白（OVA）的剂量被认为是气道高反应性（AHR）发生的关键因素。然而，目前研究中使用的致敏 OVA 剂量不一致以及缺乏对其对 AHR 影响的研究是显着的局限性。方法我们在小鼠哮喘模型中研究了增加 OVA 致敏剂量的影响，该模型需要先用 OVA 致敏，然后再使用反复暴露于 OVA 气溶胶。 BALB/c 小鼠在第 0 天和第 7 天用 OVA（0、10、20、50 和 100 μg）加 1 mg 明矾进行免疫，并在几天之间用 OVA 气雾剂（10 mg/mL，持续 30 分钟）进行攻击14和17。评估了抗原诱导的乙酰甲胆碱（MCh）AHR，以及组织学变化、嗜酸性粒细胞浸润和上皮损伤。结果结果表明，抗原诱导的MCh AHR存在显着的OVA剂量相关差异。在 50 μg 致敏时观察到最强烈的抗原诱导 AHR，而在 10、20 和 100 μg 时观察到较弱的反应。同时，50μg致敏时嗜酸性粒细胞计数显着增加。 AHR的变化与支气管肺泡灌洗液中总细胞数、淋巴细胞数、嗜酸性粒细胞数、嗜碱性粒细胞数相关；然而，它与组织学变化（如细胞浸润支气管血管束和支气管上皮杯状细胞增生）无关。结论总体而言，本研究表明，与其他剂量相比，50 μg OVA 致敏可产生最显着的 AHR。这些发现可能为小鼠哮喘建模方案的未来研究提供有价值的见解。