Transforming growth factor β1 and recruitment of macrophages and mast cells in airways in chronic obstructive pulmonary disease
Transforming growth factor β1 and recruitment of macrophages and mast cells in airways in chronic obstructive pulmonary disease
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DOI：
10.1164/ajrccm.158.6.9803053
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发表时间：
1998-12-01
影响因子：
24.7
通讯作者：
van Krieken, JHJM
中科院分区：
文献类型：
--
作者：
de Boer, WI;van Schadewijk, A;van Krieken, JHJM
慢性呼吸道炎症是慢性阻塞性肺疾病(COPD)的特征之一。我们先前证实COPD患者的细支气管上皮含有大量的巨噬细胞和肥大细胞。转化生长因子β(1)(TCF-β(1))可能参与了这种流入，因为它对巨噬细胞和肥大细胞具有趋化活性。在这项研究中，我们用免疫组织化学和原位杂交的方法检测了14例COPD患者(FEV1)和14例非COPD患者(FEV1和GT；84%)外周肺组织中转化生长因子-β(1)、转化生长因子-β受体I和II(转化生长因子-βRI和转化生长因子-β受体II)的表达模式。在这两组中，转化生长因子-β(1)及其受体存在于呼吸道和肺泡上皮细胞、气道和血管平滑肌细胞、组织和肺泡CD68(+)细胞(这里认为是巨噬细胞)。在COPD受试者中，半定量分析显示，与非COPD受试者相比，细支气管和肺泡上皮(p<；0.02)中TCF-β(1)的mRNA和蛋白水平大约高出一倍。对于细支气管上皮细胞，我们发现转化生长因子-β(1)基因和蛋白的表达之间存在显著的相关性(r=0.62p<；0.002)，所有受试者的FEV1与转化生长因子-β(1)蛋白(r=-0.60p<；0.0002)和信使核糖核酸(r=-0.67p(0.002))之间存在显著的相关性。上皮组织中TCF-β(1)mRNA和TCF-β(1)蛋白的表达与上皮内巨噬细胞数呈正相关(r=0.44；p<；0.03)，而上皮内肥大细胞数与上皮TCF-β(1)mRNA的表达呈正相关。这些数据表明，TCF-beta(1)在COPD患者的呼吸道上皮细胞募集巨噬细胞中发挥了作用。
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 beta(1) (TCF-beta(1)) 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-beta(1), TGF-beta receptors type I and II (TGF-beta RI and TGF-beta RII) 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-beta(1) 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 TCF-beta(1) 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-beta(1) mRNA and protein expression (r = 0.62; p < 0.002), and between the FEV1 of all subjects together and TCF-beta(1) protein (r = -0.60; p < 0.0002) and mRNA (r = -0.67; p ( 0.002) levels. The epithelial expression of TCF-beta(1) mRNA and TCF-beta(1) protein correlates with the number of intraepithelial macrophages (both: r = 0.44; p < 0.03) whereas intraepithelial mast cell numbers correlate with epithelial TCF-beta(1) mRNA expression. These data suggest a role for TCF-beta(1) in recruiting macrophages into the airway epithelium in COPD.