Hirota Jeremy A, Ellis Russ, Inman Mark D
Firestone Institute for Respiratory Health, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Respir Res. 2006 Sep 21;7(1):120. doi: 10.1186/1465-9921-7-120.
Airway remodeling present in the large airways in asthma or asthma models has been associated with airway dysfunction in humans and mice. It is not clear if airways distal to the large conducting airways have similar degrees of airway remodeling following chronic allergen exposure in mice. Our objective was to test the hypothesis that airway remodeling is heterogeneous by optimizing a morphometric technique for distal airways and applying this to mice following chronic exposure to allergen or saline.
In this study, BALB/c mice were chronically exposed to intranasal allergen or saline. Lung sections were stained for smooth muscle, collagen, and fibronectin content. Airway morphometric analysis of small (0-50000 microm2), medium (50000 microm2-175000 microm2) and large (>175000 microm2) airways was based on quantifying the area of positive stain in several defined sub-epithelial regions of interest. Optimization of this technique was based on calculating sample sizes required to detect differences between allergen and saline exposed animals.
Following chronic allergen exposure BALB/c mice demonstrate sustained airway hyperresponsiveness. BALB/c mice demonstrate an allergen-induced increase in smooth muscle content throughout all generations of airways, whereas changes in subepithelial collagen and fibronectin content are absent from distal airways.
We demonstrate for the first time, a systematic objective analysis of allergen induced airway remodeling throughout the tracheobronchial tree in mice. Following chronic allergen exposure, at the time of sustained airway dysfunction, BALB/c mice demonstrate regional differences in the pattern of remodeling. Therefore results obtained from limited regions of lung should not be considered representative of the entire airway tree.
哮喘或哮喘模型中大气道存在的气道重塑与人类和小鼠的气道功能障碍有关。目前尚不清楚在小鼠慢性过敏原暴露后，大气道远端的气道是否具有相似程度的气道重塑。我们的目的是通过优化一种用于远端气道的形态计量技术，并将其应用于慢性暴露于过敏原或生理盐水后的小鼠，来检验气道重塑是异质性的这一假设。
在本研究中，BALB/c小鼠被慢性鼻内暴露于过敏原或生理盐水。肺切片进行平滑肌、胶原蛋白和纤连蛋白含量染色。对小气道（0 - 50000平方微米）、中等气道（50000平方微米 - 175000平方微米）和大气道（>175000平方微米）进行气道形态计量分析，基于对几个定义的上皮下感兴趣区域的阳性染色面积进行量化。该技术的优化基于计算检测过敏原和生理盐水暴露动物之间差异所需的样本量。
慢性过敏原暴露后，BALB/c小鼠表现出持续的气道高反应性。BALB/c小鼠在所有气道代中均表现出过敏原诱导的平滑肌含量增加，而远端气道上皮下胶原蛋白和纤连蛋白含量没有变化。
我们首次展示了对小鼠整个气管支气管树中过敏原诱导的气道重塑进行系统客观分析。慢性过敏原暴露后，在持续气道功能障碍时，BALB/c小鼠在重塑模式上表现出区域差异。因此，从肺的有限区域获得的结果不应被视为代表整个气道树。
