title: Evidence of type II pneumocyte apoptosis in the pathogenesis of idiopathic pulmonary fibrosis (IFP)/usual interstitial pneumonia (UIP).
abstract: OBJECTIVE
  The pathogenesis of idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP), a chronic and incurable human respiratory disease, is not well established. This study was designed to investigate whether the apoptosis of type II pneumocytes could be the precipitating factor 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 labelling of fragmented DNA were performed on paraffin was embedded sections using digoxigenin-11-dUTP and the enzyme terminal deoxynucleotidyl transferase.
  
  
  RESULTS
  Apoptosis was detected in the normal alveoli of 17 of the 19 patients with IPF/UIP and was absent in the controls. Electron microscopy demonstrated apoptotic changes in type II 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 histological, clinical, and functional alterations seen in IPF/UIP.
  
  
  CONCLUSIONS
  In conclusion, numerous type II pneumocytes from the normal alveoli of most patients with IPF/UIP actively undergo programmed cell death. This finding may shed new light on the pathogenesis of this disease, with implications mainly for the treatment of affected patients.
authors.affiliation: Department of Pathology, University of São Paulo School of Medicine, São Paulo, CEP 01250-020, Brazil. vcapelozzi@.lim05.fm.usp.br
authors.forename: J V
authors.initials: JV
authors.lastname: Barbas-Filho
authors.forename: M A
authors.initials: MA
authors.lastname: Ferreira
authors.forename: A
authors.initials: A
authors.lastname: Sesso
authors.forename: R A
authors.initials: RA
authors.lastname: Kairalla
authors.forename: C R
authors.initials: CR
authors.lastname: Carvalho
authors.forename: V L
authors.initials: VL
authors.lastname: Capelozzi
mesh_terms: D000368:Aged; D017209:Apoptosis; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000648:ultrastructure; D011658:Pulmonary Fibrosis / Q000473:pathology*; D012189:Retrospective Studies