Temporal correlation of measurements of airway hyperresponsiveness in ovalbumin-sensitized mice
Temporal correlation of measurements of airway hyperresponsiveness in ovalbumin-sensitized mice
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DOI：
10.1152/ajplung.00324.2001
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发表时间：
2002-07-01
影响因子：
4.9
通讯作者：
McIntyre, TM
中科院分区：
文献类型：
--
作者：
Albertine, KH;Wang, L;McIntyre, TM
气道高反应性、气道炎症和可逆性气道阻塞是哮喘的生理学标志。这些反应越来越多地在抗原暴露和激发的小鼠模型中进行研究，使用全身体积描记法非侵入性地评估气道高反应性。这种方法很少与通过侵入性手段测量的气道高反应性指数相关。此外，缺乏与每日气道激发期间炎性和免疫细胞组织浸润（特别是气道壁）的定量组织学数据的相关性。为了解决这些不确定性，我们使用了C57 BL/6小鼠，这些小鼠用卵清蛋白或载体（盐水）免疫，并在8天后对雾化的卵清蛋白或载体致敏。随后在第14-22天，将小鼠分别暴露于雾化的卵清蛋白或载体。我们在第14、15、18或22天非侵入性评估了乙酰甲胆碱的气道高反应性; 24小时后，我们研究了相同的小鼠，同时它们被麻醉用于气道高反应性的侵入性分析。血浆总IgE浓度显着较高的卵清蛋白治疗的小鼠相比，溶剂治疗的小鼠，但这并不与嗜酸性粒细胞数量。通过任一方法测量的气道高反应性峰值在每日抗原激发期间（第14和15天）早期相关，但在随后的每日抗原激发期间（第18和22天），这种相关性随后消失。在第14和15天，气道高反应性峰值与支气管血管周围结缔组织鞘中的中性粒细胞和巨噬细胞的迁移相关，但与淋巴细胞无关。通过三维显微镜观察发现血管外蓄积是局灶性的。我们的结论是，虽然卵清蛋白治疗改变了小鼠的肺功能，非侵入性和侵入性的气道高反应性峰值之间的相关性是不一致的。
Airway hyperresponsiveness, airway inflammation, and reversible airway obstruction are physiological hallmarks of asthma. These responses are increasingly being studied in murine models of antigen exposure and challenge, using whole body plethysmography to noninvasively assess airway hyperresponsiveness. This approach infrequently has been correlated with indexes of airway hyperresponsiveness measured by invasive means. Furthermore, correlation with quantitative histological data for tissue infiltration by inflammatory and immune cells, particularly in the wall of airways, during daily airway challenge is lacking. To address these uncertainties, we used C57BL/6 mice that were immunized with ovalbumin or vehicle (saline) and sensitized to aerosolized ovalbumin or vehicle 8 days later. The mice were subsequently exposed to aerosolized ovalbumin or vehicle, respectively, on days 14-22. We assessed airway hyperresponsiveness to methacholine noninvasively on days 14, 15, 18, or 22; we studied the same mice 24 h later while they were anesthetized for invasive analyses of airway hyperresponsiveness. Plasma total IgE concentration was significantly higher in the ovalbumin-treated mice compared with the vehicle-treated mice, but this did not correlate with eosinophil number. Peak airway hyperresponsiveness measured by either approach correlated early during daily antigen challenge (days 14 and 15), but this correlation was lost later during subsequent daily antigen challenges (days 18 and 22). On days 14 and 15, peak airway hyperresponsiveness correlated with transmigration of neutrophils and macrophages, but not lymphocytes, in the peribronchovascular connective tissue sheaths. This extravascular accumulation was found to be focal by three-dimensional microscopy. We conclude that, although ovalbumin treatment changed lung function in mice, correlation between noninvasive and invasive measures of peak airway hyperresponsiveness was inconsistent.