Moreland L W, Goldsmith K T, Russell W J, Young K R, Garver R I
Department of Medicine, University of Alabama School of Medicine, Birmingham 35294.
Am J Med. 1992 Dec;93(6):628-36. doi: 10.1016/0002-9343(92)90195-h.
PURPOSE, PATIENTS, AND METHODS: Since transforming growth factor beta (TGF beta) has been implicated as an important mediator of pulmonary fibrosis, we measured TGF beta protein and gene expression in alveolar epithelial lining fluid (ELF) of fibrotic scleroderma lungs sampled by bronchoalveolar lavage (BAL). TGF beta protein was qualitatively examined by Western blot analysis, and quantitatively by radioreceptor assays. Gene expression was evaluated in BAL mononuclear cells by Northern blot analysis with quantification of relative gene expression by densitometric analysis of the autoradiograms.
Normal and scleroderma subjects had a 24-kd protein that comigrated with defined human TGF beta 1 and immunoreacted with anti-TGF beta antibody. The normal population had a significantly higher average TGF beta concentration (705 pM) compared with the scleroderma subjects (177 pM). The TGF beta 1 gene was expressed in amounts that did not significantly differ between the scleroderma and normal groups. On an individual subject basis, the TGF beta concentration variability did not correlate with variations in BAL cellularity or TGF beta 1 gene expression within the recovered mononuclear cells.
It is concluded that both normal and fibrotic lungs have TGF beta 1 present at the alveolar epithelial surface. However, in the fibrotic scleroderma lungs, TGF beta protein content and gene expression were not increased at the alveolar epithelial surface. The simultaneous analysis of TGF beta protein content, gene expression, and cellular constituents within individual ELF specimens showed that the cellular components of the ELF do not appear to be major determinants of TGF beta protein concentration at the alveolar epithelial surface.
目的、患者与方法：由于转化生长因子β（TGFβ）被认为是肺纤维化的重要介质，我们通过支气管肺泡灌洗（BAL）对纤维化硬皮病肺的肺泡上皮衬液（ELF）中的TGFβ蛋白和基因表达进行了检测。通过蛋白质印迹分析对TGFβ蛋白进行定性检测，并通过放射受体分析进行定量检测。通过Northern印迹分析评估BAL单核细胞中的基因表达，并通过对放射自显影片进行光密度分析来定量相对基因表达。
正常人和硬皮病患者均有一条24-kd的蛋白，其迁移率与确定的人TGFβ1一致，并与抗TGFβ抗体发生免疫反应。与硬皮病患者（177 pM）相比，正常人群的平均TGFβ浓度显著更高（705 pM）。TGFβ1基因的表达量在硬皮病组和正常组之间没有显著差异。在个体受试者层面，TGFβ浓度的变异性与回收的单核细胞中BAL细胞数量或TGFβ1基因表达的变化无关。
得出的结论是，正常肺和纤维化肺在肺泡上皮表面均存在TGFβ1。然而，在纤维化硬皮病肺中，肺泡上皮表面的TGFβ蛋白含量和基因表达并未增加。对单个ELF标本中的TGFβ蛋白含量、基因表达和细胞成分进行同步分析表明，ELF的细胞成分似乎不是肺泡上皮表面TGFβ蛋白浓度的主要决定因素。
