Does Defective Apoptosis Play A Role in Cystic Fibrosis Lung Disease?

Background and Aims

Although apoptotic dysfunction has recently been suggested in cystic fibrosis (CF), there are few studies reported concerning apoptosis in CF with controversial results. The aim of this study was to investigate apoptosis in CF human lung tissues and compare with non-CF bronchiectatic and normal healthy lung tissues. We also investigated the relation between apoptosis and histopathological features of tissues and microbiological factors influencing apoptosis.

Methods

Lung tissue samples from CF (n=30), non-CF bronchiectasis (n=28, BE group) and normal control cases (n=24, C group) were included in the study. Histological examination of H & E-stained archived slides was performed and TUNEL method was used to detect DNA fragmentation.

Results

Apoptotic alveolar epithelial cells were significantly increased in the CF group compared to BE and C groups (p=0.046). Bronchopneumonia (BP) was present in 15 CF cases (50%), whereas none of the cases in C group had BP (p=0.0001). Apoptosis was significantly increased in cases with BP (n=17) compared to cases without BP (n=65) (p=0.04).

Conclusions

Apoptotic epithelial cells and BP were significantly increased in the CF group and excess level of apoptosis may be the result of enhanced occurrence of BP. Apoptotic cells were alveolar epithelial cells in the great majority of the patients and were not detected in other locations where CFTR expression is much more prominent than alveolar cells. We may postulate that increased apoptotic findings in the alveolar epithelium were related with the presence of chronic infections rather than CFTR dysfunction.

Key Words: Apoptosis, Bronchiectasis, Bronchopneumonia, Cystic fibrosis, Lung