Research of tissue remodelling in chronic obstructive pulmonary diseases

1. 原位杂交法检测慢性支气管炎患者支气管上皮细胞、成纤维细胞和巨噬细胞中TNFalpha、TGFalpha、TGFbeta1和PDGF-B mRNA的表达量，哮喘患者支气管嗜酸性粒细胞中表达量最高。相比之下，在对照组中，很少有细胞表达TNFalpha和PDGF-B mRNA，尽管有少数细胞定位于TGFbeta1 mRNA。半定量分析表达这些mRNA的细胞密度显示：(1)支气管哮喘患者PDGF-B mRNA的细胞密度显著高于正常对照组，(2)慢性支气管炎患者TNFalpha和TGFbeta1 mRNA的细胞密度均高于哮喘对照组和正常对照组，(3)慢性支气管炎患者PDGF-B mRNA的细胞密度与哮喘对照组相同。这些结果提示，在慢性炎症性气道疾病如慢性支气管炎和支气管哮喘中，炎症部位生长因子的表达模式对形成特定的病理生理状况具有重要意义。免疫组化法在慢性支气管炎和哮喘患者支气管组织的支气管上皮细胞、内皮细胞、成纤维细胞和巨噬细胞中检测到免疫反应性TNFalpha和PDGF-B蛋白，而在正常人的支气管组织中未检测到。在支气管哮喘和慢性支气管炎患者的痰细胞中检测免疫反应性IL-5、IL-8和GM-CSF蛋白。IL-5和GM-CSF在哮喘中的阳性细胞比例大于慢性支气管炎，IL-8在慢性支气管炎中的阳性细胞比例大于哮喘。这些结果清楚地表明，在痰细胞中检测到的细胞因子表达谱反映了每种疾病的病理特征，这表明痰在分析慢性气道炎症的细胞和分子事件方面是有用的。

1. With in situ hybridization, mRNA's of TNFalpha, TGFalpha, TGFbeta1 and PDGF-B were detected in bronchial epithelial cells, fibroblasts and macrophages of bronchial tissues from patients with chronic bronchitis, and mainly in eosinophils of those from asthmatics. In contrast, in control subjects, there were few cells expressing TNFalpha and PDGF-B mRNA,although a few cells were localized with TGFbeta1 mRNA.2. Semi-quantative analysis of the density of cells expressing these mRNA's showed : (1) the cell density only for PDGF-B mRNA in bronchial asthma was significantly geater than that in normal control, (2) the density for TNFalpha and TGFbeta1 mRNA in chronic bronchitis was greater than that in either asthma or normal control, and (3) the density for PDGF-B mRNA in chronic bronchitis was as great as that in asthma. These results suggest that the pattern of growth factors expressed at the site of inflammation is important to develop the specific pathophysiological condition in chronic inflammatory airway diseases such as chronic bronchitis and bronchial asthma.3. With immunohistochemistry, immunoreactive TNFalpha and PDGF-B protein was detected in bronchial epithelial cells, endothelial cells, fibroblasts and macrophages of bronchial tissues from patients with chronic bronchitis and asthma, but not in bronchial tissues from normal subjects.4. Immunoreactive IL-5, IL-8 and GM-CSF protein was detected in sputum cells from patients with bronchial asthma and chronic bronchitis. The percentage of cells positive for IL-5 and GM-CSF in asthma was greater than that in chronic bronchitis, and the percentage for IL-8 in chronic bronchitis was greater than that in asthma. These results clearly indicate that the profile of cytokine expression detected in sputum cells reflects pathological features in each disease, suggesting the usefulness of sputum for analyzing cellular and molecular events in chronic airway inflammation.