de Boer W I, van Schadewijk A, Sont J K, Sharma H S, Stolk J, Hiemstra P S, van Krieken J H
Departments of Pulmonology and Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Am J Respir Crit Care Med. 1998 Dec;158(6):1951-7. doi: 10.1164/ajrccm.158.6.9803053.
Chronic airways inflammation is one of the features of chronic obstructive pulmonary disease (COPD). We demonstrated previously that bronchiolar epithelium in COPD contains increased numbers of macrophages and mast cells. Transforming growth factor beta1 (TGF-beta1) may be involved in this influx because it has chemotactic activity for macrophages and mast cells. In this study, we examined expression patterns of TGF-beta1, TGF-beta receptors type I and II (TGF-betaRI and TGF-betaRII) by immunohistochemistry and mRNA in situ hybridization in peripheral lung tissue of 14 current or ex-smokers with COPD (FEV1 < 75%) and 14 without COPD (FEV1 > 84%). In both groups, TGF-beta1 and its receptors are present in airway and alveolar epithelial cells, airway and vascular smooth muscle cells, and tissue and alveolar CD68(+) cells (considered herein to be macrophages). In subjects with COPD, a semiquantitative analysis revealed approximately twofold higher levels of TGF-beta1 mRNA and protein in bronchiolar and alveolar epithelium (p < 0.02) as compared with subjects without COPD. With regard to bronchiolar epithelial cells, we found a significant correlation between TGF-beta1 mRNA and protein expression (r = 0.62; p < 0.002), and between the FEV1 of all subjects together and TGF-beta1 protein (r = -0.60; p < 0.0002) and mRNA (r = -0.67; p < 0. 002) levels. The epithelial expression of TGF-beta1 mRNA and TGF-beta1 protein correlates with the number of intraepithelial macrophages (both: r = 0.44; p < 0.03) whereas intraepithelial mast cell numbers correlate with epithelial TGF-beta1 mRNA expression. These data suggest a role for TGF-beta1 in recruiting macrophages into the airway epithelium in COPD.
慢性气道炎症是慢性阻塞性肺疾病（COPD）的特征之一。我们之前证明，COPD患者的细支气管上皮中巨噬细胞和肥大细胞数量增加。转化生长因子β1（TGF-β1）可能参与了这种细胞流入，因为它对巨噬细胞和肥大细胞具有趋化活性。在本研究中，我们通过免疫组织化学和mRNA原位杂交检测了14名COPD现吸烟者或既往吸烟者（FEV1<75%）和14名无COPD者（FEV1>84%）外周肺组织中TGF-β1、I型和II型TGF-β受体（TGF-βRI和TGF-βRII）的表达模式。在两组中，TGF-β1及其受体存在于气道和肺泡上皮细胞、气道和血管平滑肌细胞以及组织和肺泡CD68(+)细胞（本文中视为巨噬细胞）中。在COPD患者中，半定量分析显示，与无COPD者相比，细支气管和肺泡上皮中TGF-β1 mRNA和蛋白水平高约两倍（p<0.02）。关于细支气管上皮细胞，我们发现TGF-β1 mRNA与蛋白表达之间存在显著相关性（r=0.62；p<0.002），所有受试者的FEV1与TGF-β1蛋白（r=-0.60；p<0.0002）和mRNA（r=-0.67；p<0.002）水平之间也存在显著相关性。TGF-β1 mRNA和TGF-β1蛋白的上皮表达与上皮内巨噬细胞数量相关（两者：r=0.44；p<0.03），而上皮内肥大细胞数量与上皮TGF-β1 mRNA表达相关。这些数据表明TGF-β1在COPD患者气道上皮中招募巨噬细胞方面发挥作用。
