Airway proteoglycans are differentially altered in fatal asthma
Airway proteoglycans are differentially altered in fatal asthma
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DOI：
10.1002/path.1818
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发表时间：
2005-09-01
影响因子：
7.3
通讯作者：
Dolhnikoff, M
中科院分区：
文献类型：
--
作者：
Matsushita, MD;da Silva, LFF;Dolhnikoff, M
研究表明，气道重塑是导致某些哮喘患者持续气道阻塞和肺功能下降的原因。小气道被认为是这种功能障碍的重要原因。蛋白聚糖（PG）是肺细胞外基质（ECM）的重要组成部分。除了控制ECM的生物物理特性外，它们在一些细胞因子的调节中起重要作用。轻度哮喘患者气道上皮下PG沉积增加已有报道。然而，没有关于哮喘小气道中PG含量的数据。本研究比较了哮喘死亡患者与正常对照肺内大、小气道前列腺素的含量和分布。使用免疫组织化学和图像分析来确定18名死于哮喘的患者（A）和10名对照（C）的大（内周长> 6 mm）和小（内周长<6 mm）气道中的光蛋白聚糖、核心蛋白聚糖、双糖蛋白聚糖和多功能蛋白聚糖的含量。结果表示为PG面积（μ m（2））/上皮基底膜长度（μ m）。哮喘患者和对照组之间的主要差异在小气道。在哮喘患者的小气道的外部区域中，核心蛋白聚糖和光蛋白聚糖含量显著降低（核心蛋白聚糖：A = 1.05 +/-0.27 μ m，C = 3.97 +/-1.17 μ m，p = 0.042;光蛋白聚糖：A = 1.97 +/-0.37 μ m，C = 5.66 +/-0.99 μ m，p = 0.002）。还观察到哮喘患者小气道和大气道内区多功能蛋白聚糖含量显著增加（小：A 7.48 +/-0.84 μ m，C = 5.16 +/-0.61 μ m，p = 0.045;大：A = 18.38 +/-1.94 μ m，C = 11.90 +/-2.86 μ m，p = 0.028）。结果表明，PGs在致命性哮喘的气道中差异表达，并可能有助于气道重塑。这些数据加强了小气道在哮喘气道重塑中的重要性。版权所有（c）2005大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
It has been suggested that airway remodelling is responsible for the persistent airway obstruction and decline in lung function observed in some asthmatic patients. The small airways are thought to contribute significantly to this functional impairment. Proteoglycans (PGs) are important components of the extracellular matrix (ECM) in the lungs. Besides controlling biophysical properties of the ECM, they play important roles in the regulation of some cytokines. Increased subepithelial PG deposition in the airways of mild asthmatics has been reported. However, there are no data on the PG content in small airways in asthma. This study has compared the content and distribution of PGs in large and small airways of patients who died of asthma with those in control lungs. Immunohistochemistry and image analysis were used to determine the content of lumican, decorin, biglycan, and versican in large (internal perimeter > 6 mm) and small (internal perimeter < 6 mm) airways of 18 patients who had died of asthma (A) and ten controls (C). The results were expressed as PG area (mu m(2))/epithelial basement membrane length (mu m). The main differences between asthmatics and controls were observed in the small airways. There was a significant decrease in decorin and lumican contents in the external area of small airways in asthmatics (decorin: A = 1.05 +/- 0.27 mu m, C = 3.97 +/- 1.17 mu m, p = 0.042; lumican: A = 1.97 +/- 0.37 mu m, C = 5.66 +/- 0.99 mu m, p = 0.002). A significant increase in versican content in the internal area of small and large airways in asthmatics was also observed (small: A 7.48 +/- 0.84 mu m, C = 5.16 +/- 0.61 mu m, p = 0.045; large: A = 18.38 +/- 1.94 mu m, C = 11.90 +/- 2.86 mu m, p = 0.028). The results show that PGs are differentially expressed in the airways of fatal asthma and may contribute to airway remodelling. These data reinforce the importance of the small airways in airway remodelling in asthma. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.