Miotto D, Hollenberg M D, Bunnett N W, Papi A, Braccioni F, Boschetto P, Rea F, Zuin A, Geppetti P, Saetta M, Maestrelli P, Fabbri L M, Mapp C E
Institute of Respiratory Diseases, University of Ferrara, Italy.
Thorax. 2002 Feb;57(2):146-51. doi: 10.1136/thorax.57.2.146.
Protease activated receptor-2 (PAR-2) is a transmembrane G protein coupled receptor preferentially activated by trypsin and tryptase. The protease activated receptors play an important role in most components of injury responses including cell proliferation, migration, matrix remodelling, and inflammation. Cigarette smoking causes an inflammatory process in the central airways, peripheral airways, lung parenchyma, and adventitia of pulmonary arteries.
To quantify the expression of PAR-2 in the central airways of smokers and non-smokers, surgical specimens obtained from 30 subjects undergoing lung resection for localised pulmonary lesions (24 with a history of cigarette smoking and six non-smoking control subjects) were examined. Central airways were immunostained with an antiserum specific for PAR-2 and PAR-2 expression was quantified using light microscopy and image analysis.
PAR-2 expression was found in bronchial smooth muscle, epithelium, glands, and in the endothelium and smooth muscle of bronchial vessels. PAR-2 expression was similar in the central airways of smokers and non-smokers. When smokers were divided according to the presence of symptoms of chronic bronchitis and chronic airflow limitation, PAR-2 expression was increased in smooth muscle (median 3.8 (interquartile range 2.9-5.8) and 1.4 (1.07-3.4) respectively); glands (33.3 (18.2-43.8) and 16.2 (11.5-22.2), respectively); and bronchial vessels (54.2 (48.7-56.8) and 40.0 (36-40.4), respectively) of smokers with symptoms of chronic bronchitis with normal lung function compared with smokers with chronic airflow limitation (COPD), but the increase was statistically significant (p<0.005) only for bronchial vessels.
PAR-2 is present in bronchial smooth muscle, glands, and bronchial vessels of both smokers and non-smokers. An increased expression of PAR-2 was found in bronchial vessels of patients with bronchitis compared with those with COPD.
蛋白酶激活受体-2(PAR-2)是一种跨膜G蛋白偶联受体,优先被胰蛋白酶和类胰蛋白酶激活。蛋白酶激活受体在损伤反应的大多数成分中发挥重要作用,包括细胞增殖、迁移、基质重塑和炎症。吸烟会在中央气道、外周气道、肺实质和肺动脉外膜引发炎症过程。
为了量化吸烟者和非吸烟者中央气道中PAR-2的表达,对30例因局限性肺部病变接受肺切除术的患者(24例有吸烟史,6例为非吸烟对照者)的手术标本进行了检查。用针对PAR-2的抗血清对中央气道进行免疫染色,并使用光学显微镜和图像分析对PAR-2表达进行量化。
在支气管平滑肌、上皮、腺体以及支气管血管的内皮和平滑肌中发现了PAR-2表达。吸烟者和非吸烟者中央气道中的PAR-2表达相似。当根据慢性支气管炎和慢性气流受限症状的有无对吸烟者进行分类时,与患有慢性气流受限(慢性阻塞性肺疾病,COPD)的吸烟者相比,肺功能正常的慢性支气管炎症状吸烟者的平滑肌中PAR-2表达增加(中位数分别为3.8(四分位间距2.9 - 5.8)和1.4(1.07 - 3.4));腺体中PAR-2表达增加(分别为33.3(18.2 - 43.8)和16.2(11.5 - 22.2));支气管血管中PAR-2表达增加(分别为54.2(48.7 - 56.8)和40.0(36 - 40.4)),但仅支气管血管中的增加具有统计学意义(p<0.005)。
PAR-2存在于吸烟者和非吸烟者的支气管平滑肌、腺体和支气管血管中。与COPD患者相比,支气管炎患者支气管血管中PAR-2表达增加。