Airway hyperreactivity is associated with specific leukocyte subset infiltration in a mouse model of allergic airway inflammation.
Airway hyperreactivity is associated with specific leukocyte subset infiltration in a mouse model of allergic airway inflammation.
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过敏性气道炎症小鼠模型中，气道高反应性与特定白细胞亚群浸润相关。
DOI：
10.1159/000164065
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Albert,RK
中科院分区：
文献类型：
--
作者：
Lukacs,NW;Lamm,WJ;Strieter,RM;Albert,RK
气道高反应性被定义为对物理、药理或其他刺激的支气管收缩反应增加。哮喘患者发生气道高反应性以及支气管周围炎症。我们采用了一个已建立的可溶性虫卵抗原（SEA）诱导的小鼠过敏性气道炎症模型来研究气道高反应性和白细胞亚群浸润之间的时间关系。在小鼠中使用静脉注射乙酰甲胆碱的剂量反应曲线来表征鼻内SEA再激发后不同时间点的气道反应性。通过支气管肺泡灌洗评估进入空气空间的细胞浸润。气道高反应性早在攻击后1小时增加。高反应性峰值出现在攻毒后8 h。随后，反应性在24 h时降低，并在48 h时降至对照组中观察到的水平。中性粒细胞内流与气道反应性的增加直接相关，因为早在1小时就观察到中性粒细胞，在8小时达到峰值，在24小时减少，并且在SEA攻击后48小时未检测到。相比之下，嗜酸性粒细胞浸润，直到24小时，并在48小时达到高峰后，SEA再激发时，气道反应性的增加没有检测到。乙酰甲胆碱诱导的气道阻力与中性粒细胞浸润相关（r2= 0.90），但与嗜酸性粒细胞浸润无关（r2= 0.1）。这些结果表明，在过敏性气道炎症过程中观察到的气道高反应性与气道嗜酸性粒细胞相关，与嗜酸性粒细胞聚集弱。
Airway hyperreactivity is defined as an increased bronchoconstrictor response to physical, pharmacological, or other stimuli. Patients with asthma develop airway hyperreactivity as well as peribronchial inflammation. We employed an established schistosome soluble egg antigen (SEA)-induced murine model of allergic airway inflammation to examine the temporal relationship between airway hyperreactivity and leukocyte subset infiltration. Dose response curves of intravenous methacholine were used in mice to characterize airway reactivity at various time points after intranasal SEA rechallenge. Cellular infiltration into the airspace was assessed by bronchoalveolar lavage. Airway hyperreactivity increased as early as 1 h postchallenge. Peak hyperreactivity occurred at 8 h postchallenge. Subsequently, reactivity decreased at 24 h and fell to the level observed in controls by 48 h. Neutrophil influx correlated directly with the increase in airway reactivity, as neutrophils were observed as early as 1 h, peaked at 8 h, diminished by 24 h and were not detected at 48 h post-SEA challenge. In contrast, eosinophil infiltration was not observed until 24 h and peaked at 48 h post-SEA rechallenge when increases in airway reactivity were not detected. Airway resistance induced by methacholine correlated with neutrophil (r2= 0.90) but not eosinophil (r2= 0.1) infiltration. These results suggest that the airway hyperreactivity observed during allergic airway inflammation correlates with airway neutrophilia and weakly with eosinophil accumulation.