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比较变应性气道炎症和高反应性小鼠模型中的气溶胶和鼻内激发。

Comparison of aerosol and intranasal challenge in a mouse model of allergic airway inflammation and hyperresponsiveness.

机构信息

The National Institute of Environmental Medicine, Division of Physiology, and The Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.

出版信息

Int Arch Allergy Immunol. 2010;153(3):249-58. doi: 10.1159/000314365. Epub 2010 May 19.

Abstract

BACKGROUND

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.

METHOD

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

方法

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。

结果

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。

结论

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。

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