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.
Baptista
Aline Lourenso
AL
Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.
Parra
Edwin Roger
ER
Filho
João Valente Barbas
JV
Kairalla
Ronaldo Adib
RA
de Carvalho
Carlos Roberto Ribeiro
CR
Capelozzi
Vera Luiza
VL
D000368:Aged; D004847:Epithelial Cells / Q000473:pathology; D004848:Epithelium / Q000473:pathology / Q000502:physiology; D005260:Female; D006801:Humans; D008168:Lung / Q000502:physiology; D017563:Lung Diseases, Interstitial / Q000473:pathology*; D008297:Male; D008875:Middle Aged