Baptista Aline Lourenso, Parra Edwin Roger, Filho João Valente Barbas, Kairalla Ronaldo Adib, de Carvalho Carlos Roberto Ribeiro, Capelozzi Vera Luiza
Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.
Lung. 2006 Jul-Aug;184(4):239-44. doi: 10.1007/s00408-005-2585-9.
Epithelial remodeling probably contributes to parenchymal deterioration in usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF), but understanding its mechanisms is still a challenge. The aim of our study was to examine apoptosis and the epithelial changes in the histologic pattern of UIP. After immunohistochemical staining we quantified the content of type I cells, type II cells, surfactant-A protein, bcl-2, and Fas-ligand (Fas-L) in control and alveolar collapse, fibroblastic foci, and honeycomb in UIP areas of 23 open lung biopsies. A significant association was found between epithelial changes and parenchymal deterioration (p < 0.05). Type I epithelial cell density was similar between control (1.7 +/- 0.7%) and UIP alveolar collapse areas (1.8 +/- 0.6%) but decreased progressively in fibroblastic foci zones (0.8 +/- 0.4%) and honeycomb changes (0.4 +/- 0.3%). Type II cell density increased from control (25.6 +/- 8.3%) to areas of alveolar collapse (34.5 +/- 11.4%), then decreased toward fibroblastic foci (15.4 +/- 6.0%) and honeycomb change areas (23.1 +/- 8.6%). The surfactant-A protein increased from control (6.7 +/- 3.2%) to areas of alveolar collapse (31.1 +/- 9.5%) and decreased toward fibroblastic foci (14.5 +/- 4.9%) and honeycomb change areas (21.1 +/- 8.9%). Fas-L positive epithelial cell density presented a progressive decline from control (48.5 +/- 9.5%), alveolar collapse (37.9 +/- 12.4%), fibroblastic foci (27.4 +/- 6.8%), and honeycomb change areas (21.9 +/- 6.5%). A similar decline in density was found for bcl-2 positive epithelial cells from control (20.4 +/- 2.7%), alveolar collapse (18.9 +/- 5.1%), and fibroblastic foci areas (13.8 +/-2.9%), then increased honeycomb change areas (16.3 +/- 2.8%). We conclude that loss of the nuclear (bcl-2) and membrane (Fas-L) regulation of normal cell population density and suppression of cell death by apoptosis in UIP may be a determinant of the abnormal epithelial/parenchymal remodeling in UIP.
上皮重塑可能导致寻常型间质性肺炎/特发性肺纤维化（UIP/IPF）的实质恶化，但了解其机制仍是一项挑战。我们研究的目的是检查UIP组织学模式中的细胞凋亡和上皮变化。免疫组化染色后，我们对23例开胸肺活检UIP区域的对照、肺泡塌陷、成纤维细胞灶和蜂窝状区域中I型细胞、II型细胞、表面活性蛋白A、bcl-2和Fas配体（Fas-L）的含量进行了定量分析。发现上皮变化与实质恶化之间存在显著关联（p<0.05）。对照（1.7±0.7%）和UIP肺泡塌陷区域（1.8±0.6%）的I型上皮细胞密度相似，但在成纤维细胞灶区域（0.8±0.4%）和蜂窝状改变区域（0.4±0.3%）逐渐降低。II型细胞密度从对照（25.6±8.3%）增加到肺泡塌陷区域（34.5±11.4%），然后向成纤维细胞灶（15.4±6.0%）和蜂窝状改变区域（23.1±8.6%）降低。表面活性蛋白A从对照（6.7±3.2%）增加到肺泡塌陷区域（31.1±9.5%），并向成纤维细胞灶（14.5±4.9%）和蜂窝状改变区域（21.1±8.9%）降低。Fas-L阳性上皮细胞密度从对照（48.5±9.5%）、肺泡塌陷（37.9±12.4%）、成纤维细胞灶（27.4±6.8%）到蜂窝状改变区域（21.9±6.5%）呈逐渐下降趋势。bcl-2阳性上皮细胞密度从对照（20.4±2.7%）、肺泡塌陷（18.9±5.1%）和成纤维细胞灶区域（13.8±2.9%）也有类似的下降，然后在蜂窝状改变区域增加（16.3±2.8%）。我们得出结论，UIP中核（bcl-2）和膜（Fas-L）对正常细胞群体密度的调节丧失以及细胞凋亡对细胞死亡的抑制可能是UIP中上皮/实质异常重塑的一个决定因素。
