Evidence of type II pneumocyte apoptosis in the pathogenesis of idiopathicpulmonary fibrosis (IFP)/usual interstitial pneumonia (UIP)

Background/Aims-The pathogenesis of idiopathic pulmonary fibrosis (IPF)/usu al interstitial pneumonia (UIP), a chronic and incurable human respiratory disease, is not well established. This study was designed to investigate wh ether the apoptosis of type PI pneumocytes could be the precipitating facto r in the pathogenesis of IPF. Methods-Nineteen specimens obtained by retrospective review of the medical and pathological records of 55 patients with IPF, four normal subjects, and 10 disease control lungs were analysed. The selected specimens had normal alveoli with intervening patchy scarring of the lung parenchyma, fulfilling the pathological criteria for UIP. To identify individual cells undergoing apoptosis in the normal alveoli, electron microscopy and in situ end label ling of fragmented DNA were performed on paraffin wax embedded sections usi ng digoxigenin-11-dUTP and the enzyme terminal deoxynucleotidyl transferase . Results-Apoptosis was detected in the normal alveoli of 17 of the 19 patien ts with IPF/UIP and was absent in the controls. Electron microscopy demonst rated apoptotic changes in type PI pneumocytes. These results indicate that apoptotic type II pneumocyte death occurs in normal alveoli of IPF/UIP and could be the principal cause of several events that account for the histol ogical, clinical, and functional alterations seen in IPF/UIP. Conclusions-In conclusion, numerous type II pneumocytes from the normal alv eoli of most patients with IPF/UIP actively undergo programmed cell death. This finding may shed new light on the pathogenesis of this disease, with i mplications mainly for the treatment of affected patients.