Reduced lung function in a chronic asthma model is associated with prolonged inflammation, but independent of peribronchial fibrosis.
Reduced lung function in a chronic asthma model is associated with prolonged inflammation, but independent of peribronchial fibrosis.
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DOI：
10.1371/journal.pone.0001575
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发表时间：
2008-02-06
期刊：
影响因子：
3.7
通讯作者：
Schwarze J
中科院分区：
文献类型：
--
作者：
Koerner-Rettberg C;Doths S;Stroet A;Schwarze J
在哮喘中，导致慢性化的机制仍有待确定。最近的模型与长期的气道过敏原挑战致敏再现慢性哮喘的典型特征。然而，炎症，结构变化和肺功能之间的相互作用知之甚少。本研究旨在描述停止长期激发后的功能、结构和免疫气道变化，以阐明导致长期肺功能变化的因素。用卵白蛋白连续鼻内激发全身致敏小鼠2周或8周。激发结束后，监测肺功能、气道炎症、气道重塑特征、局部T细胞细胞因子和全身卵清蛋白特异性抗体。长期激发导致气道高反应性持续2周，停止后基线肺功能降低6周。相比之下，这些变化在短期挑战后一周内解决。仅通过长期激发诱导延长的转化生长因子β（TGF-β）1产生和显著的支气管周围纤维化。重要的是，纤维化仅在肺功能变化开始后才变得明显，并持续时间超过它们。此外，长期的挑战导致长期和强烈的气道炎症与显着的淋巴细胞增多症，但中度嗜酸性粒细胞增多症，持续的IL-5的生产和卵清蛋白特异性IgG 2a抗体，后者表明免疫应答的Th 1成分。相比之下，在短期挑战后，气道炎症由嗜酸性粒细胞主导，并与强烈但短暂的IL-13应答相关。长期过敏原激发后的肺功能改变似乎独立于持续性支气管周围纤维化而发展和消退。它们与强烈的气道炎症、显著的淋巴细胞增多、气道中IL-5和TGF-β1产生延长以及Th 1免疫应答更密切相关。
In asthma, mechanisms contributing to chronicity remain to be determined. Recent models of sensitisation with prolonged airway allergen challenges reproduce typical features of chronic asthma. However, the interplay between inflammation, structural changes and lung function is poorly understood. This study was performed to delineate functional, structural and immunological airway changes after cessation of long term challenges to elucidate factors contributing to the development of prolonged lung function changes. Mice sensitised systemically were consecutively challenged intranasally with ovalbumin for two or eight weeks. After the end of challenges, lung function, airway inflammation, features of airway remodelling, local T-cell cytokines and systemic ovalbumin-specific antibodies were monitored. Long term challenges resulted in airway hyperresponsiveness lasting 2 weeks and reduced baseline lung function for 6 weeks after their cessation. In contrast, these changes resolved within one week after short term challenges. Prolonged transforming growth factor beta (TGF-β)1 production and marked peribronchial fibrosis were only induced by long term challenges. Importantly, fibrosis became apparent only after the onset of lung function changes and outlasted them. Further, long term challenges led to prolonged and intense airway inflammation with marked lymphocytosis, but moderate eosinophilia, sustained IL-5 production and ovalbumin-specific IgG2a antibodies, the latter suggesting a Th1 component to the immune response. In contrast, following short term challenges airway inflammation was dominated by eosinophils and associated with a strong, but transient IL-13 response. Prolonged lung function changes after long term allergen challenges seem to develop and resolve independently of the persistent peribronchial fibrosis. They are more closely associated with intense airway inflammation, marked lymphocytosis, prolonged IL-5 and TGF-β1 production in the airways and a Th1 immune response.
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DOI：
10.1164/rccm.200311-1488oc
发表时间：
2004-10-15
影响因子：
24.7
作者：
Leigh, R;Ellis, R;Inman, MD
通讯作者：
Inman, MD
DOI：
10.1111/j.1365-2222.2004.01895.x
发表时间：
2004-03
期刊：
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
影响因子：
--
作者：
McMillan SJ;Lloyd CM
通讯作者：
Lloyd CM
影响因子：
14.2
作者：
Jain, VV;Kitagaki, K;Kline, JN
通讯作者：
Kline, JN
DOI：
10.1164/rccm.200308-1094oc
发表时间：
2004-02-01
影响因子：
24.7
作者：
Johnson, JR;Wiley, RE;Jordana, M
通讯作者：
Jordana, M
DOI：
10.1165/ajrcmb.17.3.2733
发表时间：
1997-09-01
影响因子：
6.4
作者：
Minshall, EM;Leung, DYM;Hamid, Q
通讯作者：
Hamid, Q