Structural features of epithelial remodeling in usual interstitial pneumonia histologic pattern

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.