The National Institute of Environmental Medicine, Division of Physiology, and The Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
Int Arch Allergy Immunol. 2010;153(3):249-58. doi: 10.1159/000314365. Epub 2010 May 19.
The aim was to optimize antigen challenge for induction of airway hyperresponsiveness (AHR) and inflammation in BALB/c mice sensitized to ovalbumin (OVA). Comparisons were made between mice challenged with OVA either as an aerosol or intranasally. The protocol that induced maximal AHR in BALB/c mice was thereafter tested in C57BL/6 mice.
Methacholine responsiveness was measured using the flexiVent® system to assess AHR. Inflammatory responses were investigated by histology and cell counts in bronchoalveolar lavage (BAL) fluid.
48 h after challenge with 1 or 6% OVA aerosols, there were similar increments in AHR and BAL cells, predominantly eosinophils. When comparing the effect of 1% OVA aerosol on AHR and cell infiltration at 24 and 48 h after challenge, the responses were similar. At 24 h, intranasal OVA administration (20-200 μg) caused a dose-dependent increase in AHR. BAL cells were increased by all intranasal OVA doses and to a greater extent than after 1% OVA aerosol challenge but without any dose dependency. Histological examination confirmed that there was an increase of eosinophils in lung tissue following either challenge. In C57BL/6 mice, baseline tissue elastance was the only functional outcome that was increased after intranasal OVA challenge. Even though the AHR response was negligible in C57BL/6 mice, a similar infiltration of BAL cells was observed in both strains.
Intranasal challenge was more effective than aerosol challenge at inducing both AHR and airway inflammation in BALB/c mice. Although intranasal challenge caused airway inflammation in C57BL/6 mice, this strain is not optimal for studying AHR.
本研究旨在优化卵清蛋白(OVA)致敏 BALB/c 小鼠气道高反应性(AHR)和炎症的抗原激发方法,比较了经雾化或经鼻激发OVA 后小鼠的 AHR 和炎症反应。此后,我们用该方案检测了 C57BL/6 小鼠的 AHR。
使用 flexiVent®系统检测乙酰甲胆碱反应性,评估 AHR;通过支气管肺泡灌洗液(BAL)中的组织学和细胞计数,研究炎症反应。
雾化吸入 1%或 6%OVA 48 h 后,AHR 和 BAL 细胞(主要是嗜酸性粒细胞)均显著增加。比较雾化吸入 1%OVA 后 24 和 48 h 的 AHR 和细胞浸润效应,两者反应相似。24 h 时,经鼻给予 20-200 μg OVA 可引起剂量依赖性 AHR 增加。所有经鼻 OVA 剂量均增加 BAL 细胞,但增加程度大于 1%OVA 雾化吸入,且无剂量依赖性。组织学检查证实,两种激发方式均可导致肺组织嗜酸性粒细胞增加。在 C57BL/6 小鼠中,经鼻 OVA 激发后,只有气道组织弹性阻力这一功能指标增加。尽管 C57BL/6 小鼠的 AHR 反应可忽略不计,但两种品系的 BAL 细胞浸润均相似。
与雾化吸入相比,经鼻激发更能有效诱导 BALB/c 小鼠的 AHR 和气道炎症。虽然经鼻激发可引起 C57BL/6 小鼠气道炎症,但该品系不适合用于研究 AHR。