Woodruff Prescott G, Dolganov Gregory M, Ferrando Ronald E, Donnelly Samantha, Hays Steven R, Solberg Owen D, Carter Roderick, Wong Hofer H, Cadbury Peggy S, Fahy John V
Division of Pulmonary and Critical Care Medicine, Department of Medicine, and Cardiovascular Research Institute, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, USA.
Am J Respir Crit Care Med. 2004 May 1;169(9):1001-6. doi: 10.1164/rccm.200311-1529OC. Epub 2004 Jan 15.
Bronchial hyperresponsiveness in mild to moderate asthma may result from airway smooth muscle cell proliferation or acquisition of a hypercontractile phenotype. Because these cells have not been well characterized in mild to moderate asthma, we examined the morphometric and gene expression characteristics of smooth muscle cells in this subgroup of patients with asthma. Using bronchial biopsies from 14 subjects with mild to moderate asthma and 15 control subjects, we quantified smooth muscle cell morphology by stereology and the expression of a panel of genes related to a hypercontractile phenotype of airway smooth muscle, using laser microdissection and two-step real-time polymerase chain reaction. We found that airway smooth muscle cell size was similar in both groups, but cell number was nearly twofold higher in subjects with asthma (p = 0.03), and the amount of smooth muscle in the submucosa was increased 50-83% (p < 0.005). Gene expression profiling in smooth muscle cells showed no difference in the expression of genes encoding phenotypic markers in cells from healthy subjects and subjects with asthma (all p > 0.1). We conclude that airway smooth muscle proliferation is a pathologic characteristic of subjects with mild to moderate asthma. However, smooth muscle cells in mild to moderate asthma do not show hypertrophy or gene expression changes of a hypercontractile phenotype observed in vitro.
轻度至中度哮喘患者的支气管高反应性可能源于气道平滑肌细胞增殖或获得高收缩表型。由于在轻度至中度哮喘中这些细胞尚未得到充分表征，我们研究了该亚组哮喘患者平滑肌细胞的形态计量学和基因表达特征。我们使用14例轻度至中度哮喘患者和15例对照受试者的支气管活检标本，通过体视学量化平滑肌细胞形态，并使用激光显微切割和两步实时聚合酶链反应，检测一组与气道平滑肌高收缩表型相关的基因表达。我们发现两组气道平滑肌细胞大小相似，但哮喘患者的细胞数量几乎高出两倍（p = 0.03），黏膜下层平滑肌量增加了50 - 83%（p < 0.005）。平滑肌细胞的基因表达谱显示，健康受试者和哮喘患者细胞中编码表型标志物的基因表达无差异（所有p > 0.1）。我们得出结论，气道平滑肌增殖是轻度至中度哮喘患者的病理特征。然而，轻度至中度哮喘患者的平滑肌细胞未表现出体外观察到的高收缩表型的肥大或基因表达变化。
