蟑螂过敏原诱导远系繁殖小鼠双相哮喘样肺部炎症
2012/07/05
摘要
目的：本试验旨在蟑螂过敏原（CRA）致敏和激发的远系繁殖小鼠中研究肺部炎症反应的动力学。
方法：在无佐剂的情况下，通过3次CRA暴露，诱导哮喘样肺部炎症。小鼠在多个时间点处死后，对哮喘样肺部炎症进行定量分析。
结果：肺部的参数显示，早期阶段（激发后1.5 h）和晚期阶段（激发后24 h）呈现明显的双向炎症性反应。早期阶段表现为多种炎症介质的产生，包括CXC趋化因子和中性粒细胞在肺部的浸润。肺嗜酸性粒细胞在早期相下降，但很快重新增加。早期阶段和晚期阶段，除了气道高反应性外，还有TNF的产生增加。该模型还显示，早期阶段产生的粘蛋白在12 h时得到清除，但最后粘蛋白又在肺上皮细胞重新积聚。肺内嗜酸细胞活化趋化因子在12 h达到峰值，肺内嗜酸性粒细胞数在研究的48 h维持相对恒定。
结论：临床相关过敏原致敏和激发后，肺部炎症参数呈现双相表现。这些结果可用于研究哮喘的致病机理，开发出针对不同阶段的靶向治疗。
(林江涛 审校)
J Asthma. 2012 Apr 30. [Epub ahead of print]
J Asthma. 2012 Apr 30. [Epub ahead of print]
Source
Department of Pathology and Laboratory Medicine, Boston University School of Medicine , Boston, MA , USA.
Abstract
OBJECTIVES：The aim of this study is to define the kinetics of the pulmonary inflammatory response in cockroach allergen (CRA) sensitized and challenged outbred mice.
METHODS：Asthma-like pulmonary inflammation was induced with three pulmonary exposures to CRA, without the use of adjuvants. Mice were sacrificed at multiple time points and asthma-like pulmonary inflammation quantified.
RESULTS：Several pulmonary parameters showed a pronounced biphasic inflammatory response with an early stage (1.5 hours post challenge) and late stage (24 hours). The initial phase was characterized by the production of multiple inflammatory mediators, including CXC chemokines, and the recruitment of neutrophils to the lung. The number of pulmonary eosinophils decreased in the early phase but quickly rebounded. Both the early and late phases had increases in TNF production in addition to airways hyperreactivity. The model also demonstrated early production of mucin with clearance by 12 hours followed by new accumulation of mucin in the pulmonary epithelial cells. Eotaxins within the lung peaked at about 12 hours and the numbers of eosinophils in the lung remained constant throughout the 48 hours of the study.
CONCLUSIONS：The pulmonary inflammatory parameters in response to a clinically relevant allergen define a biphasic response. These data may be used to investigate the pathogenesis of the disease and develop targeted therapies for the distinct phases.
J Asthma. 2012 Apr 30. [Epub ahead of print]
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过敏性哮喘患者支气管肺泡灌洗液外切酶体与细胞因子和白三烯的产生
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儿童哮喘治疗转归与血管内皮生长因子A （VEGFA）多态性相关
