Division of Respiratory Disease, Department of Clinical and Biological Sciences, A.O.U. San Luigi Hospital, University of Torino, Orbassano, Torino, Italy.
Thorax. 2013 Sep;68(9):803-11. doi: 10.1136/thoraxjnl-2012-202741. Epub 2013 Jun 5.
Vascular remodelling plays a central role in asthma and chronic obstructive pulmonary disease (COPD). Bradykinin (BK) is a vasoactive proinflammatory peptide mediating acute responses in asthma. We investigated the role of angiogenic factors in relation to BK receptors in asthma and COPD.
Bronchial biopsies from 33 patients with COPD, 24 old (≥50 years) patients with (≥50 years) asthma, 18 old control smokers, 11 old control non-smokers, 15 young (≤40yrs) patients with (≤40 years) asthma and 10 young control non-smokers were immunostained for CD31, vascular endothelial growth factor-A (VEGF-A), angiogenin and BK receptors (B2R and B1R). Fibroblast and endothelial co-localisation of relevant molecules were performed by immunofluorescence. BK-induced VEGF-A and angiogenin release was studied (ELISA) in bronchial fibroblasts from subjects with asthma and COPD.
In bronchial lamina propria of old patients with asthma, CD31 and VEGF-A(+) cell numbers were higher than old control non-smokers (p<0.05). Angiogenin(+), B2R(+) and B1R(+) cell numbers in old patients with asthma were higher than in old control non-smokers, control smokers and patients with COPD (p<0.01). Angiogenin(+) cell numbers were higher in patients with COPD than both old control groups (p<0.05). In all patients with asthma the number of B2R(+) cells was positively related to the numbers of B1R(+) (rs=0.43), angiogenin(+) (rs=0.42) and CD31 cells (rs=0.46) (p<0.01). Angiogenin(+) cell numbers were negatively related to forced expiratory volume in 1 s (rs=-0.415, p=0.008). Double immunofluorescence revealed that CD31 cells of capillary vessels coexpressed B2R and that fibroblasts coexpressed B2R, VEGF-A and angiogenin. BK (10(-6)M) induced significant angiogenin release in fibroblasts from asthma and to a lesser extent in COPD.
Unlike COPD, this study suggests the involvement of BK receptors in bronchial vascular remodelling in asthma.
血管重塑在哮喘和慢性阻塞性肺疾病（COPD）中起着核心作用。缓激肽（BK）是一种血管活性促炎肽，介导哮喘的急性反应。我们研究了血管生成因子与哮喘和 COPD 中 BK 受体的关系。
对 33 例 COPD 患者、24 例老年（≥50 岁）哮喘患者、18 例老年对照吸烟者、11 例老年对照非吸烟者、15 例年轻（≤40 岁）哮喘患者和 10 例年轻对照非吸烟者的支气管活检标本进行 CD31、血管内皮生长因子-A（VEGF-A）、血管生成素和 BK 受体（B2R 和 B1R）免疫染色。通过免疫荧光法进行成纤维细胞和相关分子的内皮共定位。研究了哮喘和 COPD 患者支气管成纤维细胞中 BK 诱导的 VEGF-A 和血管生成素释放（ELISA）。
在老年哮喘患者的支气管固有层中，CD31 和 VEGF-A（+）细胞数高于老年对照非吸烟者（p<0.05）。老年哮喘患者的血管生成素（+）、B2R（+）和 B1R（+）细胞数高于老年对照非吸烟者、对照吸烟者和 COPD 患者（p<0.01）。与两组老年对照组相比，COPD 患者的血管生成素（+）细胞数更高（p<0.05）。在所有哮喘患者中，B2R（+）细胞数与 B1R（+）（rs=0.43）、血管生成素（+）（rs=0.42）和 CD31 细胞（rs=0.46）呈正相关（p<0.01）。血管生成素（+）细胞数与用力呼气量第一秒（rs=-0.415，p=0.008）呈负相关。双重免疫荧光显示，毛细血管的 CD31 细胞共表达 B2R，成纤维细胞共表达 B2R、VEGF-A 和血管生成素。BK（10（-6）M）在哮喘和 COPD 患者的成纤维细胞中诱导明显的血管生成素释放。
与 COPD 不同，本研究表明 BK 受体参与哮喘支气管血管重塑。
