PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
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）发展的关键因素。然而,目前研究中使用的致敏OVA剂量不一致,以及缺乏关于其对AHR影响的研究是显著的局限性.
方法：我们研究了增加OVA致敏剂量对小鼠哮喘模型的影响，这需要用OVA进行初始致敏，然后反复暴露于OVA气溶胶。在第0天和第7天用剂量的OVA(0、10、20、50和100μg)加Img明矾引发BALB/c小鼠,并在第14天和第17天之间用OVA气雾剂(10mg/mL,30分钟)攻击。抗原诱导的乙酰甲胆碱（MCh）的AHR，以及组织学变化，嗜酸性粒细胞浸润,评估上皮损伤。
结果：结果表明，抗原诱导的AHR与MCh之间存在惊人的OVA剂量相关差异。在50μg的致敏中观察到最强的抗原诱导的对MCh的AHR，而在10、20和100μg时观察到较弱的反应。同时,在50μg致敏时，嗜酸性粒细胞计数显着增加。AHR的变化与细胞总数有关，淋巴细胞计数,嗜酸性粒细胞计数,支气管肺泡灌洗液中的嗜碱性粒细胞计数；然而，它与组织学变化无关，例如支气管血管束的细胞浸润和支气管上皮杯状细胞增生。
结论：总体而言，这项研究表明，与其他剂量相比，用50μgOVA致敏导致最显著的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。
方法：我们研究了增加OVA致敏剂量对小鼠哮喘模型的影响，这需要用OVA进行初始致敏，然后反复暴露于OVA气溶胶。在第0天和第7天用剂量的OVA(0、10、20、50和100μg)加Img明矾引发BALB/c小鼠,并在第14天和第17天之间用OVA气雾剂(10mg/mL,30分钟)攻击。抗原诱导的乙酰甲胆碱（MCh）的AHR，以及组织学变化，嗜酸性粒细胞浸润,评估上皮损伤。
结果：结果表明，抗原诱导的AHR与MCh之间存在惊人的OVA剂量相关差异。在50μg的致敏中观察到最强的抗原诱导的对MCh的AHR，而在10、20和100μg时观察到较弱的反应。同时,在50μg致敏时，嗜酸性粒细胞计数显着增加。AHR的变化与细胞总数有关，淋巴细胞计数,嗜酸性粒细胞计数,支气管肺泡灌洗液中的嗜碱性粒细胞计数；然而，它与组织学变化无关，例如支气管血管束的细胞浸润和支气管上皮杯状细胞增生。
结论：总体而言，这项研究表明，与其他剂量相比，用50μgOVA致敏导致最显著的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。
