Huang J, Olivenstein R, Taha R, Hamid Q, Ludwig M
Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
Am J Respir Crit Care Med. 1999 Aug;160(2):725-9. doi: 10.1164/ajrccm.160.2.9809040.
Increased extracellular matrix (ECM) deposition in the airway wall contributes to the airway wall remodeling observed in asthmatics. Although alterations in collagen have been well described, less is known about changes in other components of the ECM, particularly proteoglycans (PGs). Endobronchial biopsies were obtained from seven patients with mild atopic asthma and six normal control subjects. Tissues were blocked in OCT and frozen in isopentane. Sections were immunostained with antibodies for the small leucine-rich PGs, lumican, biglycan, decorin, and fibromodulin and for versican, a large chondroitin sulfate PG. We calculated the area of positive staining in the subepithelial layer, correcting for basement membrane length. Lumican, biglycan, and versican were localized predominantly in the subepithelial layer of the airway wall in all groups. PG deposition was significantly increased in asthmatics as compared with that in control subjects. Furthermore, the degree of PG immunoreactivity was significantly correlated with airway responsiveness in the asthmatics (lumican; r = -0.77, p < 0.05; biglycan: r = -0.76, p < 0.05; versican: r = -0.74, p = 0.06). Our results suggest that PGs may play a role in airway wall remodeling and thereby, airway mechanics in asthma.
气道壁中细胞外基质(ECM)沉积增加会导致哮喘患者出现气道壁重塑。尽管胶原蛋白的改变已得到充分描述,但对于ECM其他成分的变化,尤其是蛋白聚糖(PGs),人们了解较少。从7名轻度特应性哮喘患者和6名正常对照受试者获取支气管活检组织。组织用OCT包埋并在异戊烷中冷冻。切片用针对富含亮氨酸的小分子PGs、核纤层蛋白、双糖链蛋白聚糖、饰胶蛋白聚糖和纤调蛋白的抗体以及针对多功能蛋白聚糖(一种大型硫酸软骨素PG)的抗体进行免疫染色。我们计算了上皮下层阳性染色的面积,并根据基底膜长度进行校正。在所有组中,核纤层蛋白、双糖链蛋白聚糖和多功能蛋白聚糖主要定位于气道壁的上皮下层。与对照受试者相比,哮喘患者的PG沉积显著增加。此外,哮喘患者中PG免疫反应程度与气道反应性显著相关(核纤层蛋白;r = -0.77,p < 0.05;双糖链蛋白聚糖:r = -0.76,p < 0.05;多功能蛋白聚糖:r = -0.74,p = 0.06)。我们的结果表明,PGs可能在哮喘气道壁重塑及由此产生的气道力学中发挥作用。