title: Marked alveolar apoptosis/proliferation imbalance in end-stage emphysema.
abstract: BACKGROUND
  Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema.
  
  
  METHODS
  In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 alpha1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplantations. Six unused donor lungs served as controls. Apoptosis was evaluated by TUNEL analysis, single-stranded DNA laddering, electron microscopy and cell proliferation by an immunohistochemical method (MIB1). The role of the transforming growth factor (TGF)-beta1 pathway was also investigated and correlated with epithelial cell turnover and with the severity of inflammatory cell infiltrate.
  
  
  RESULTS
  The apoptotic index (AI) was significantly higher in emphysematous lungs compared to the control group (p < or = 0.01), particularly if only lungs with AAT-deficiency emphysema were considered (p < or = 0.01 vs p = 0.09). The proliferation index was similar in patients and controls (1.9 +/- 2.2 vs 1.7 +/- 1.1). An increased number of T lymphocytes was observed in AAT-deficiency lungs than smoking-related cases (p < or = 0.05). TGF-beta1 expression in the alveolar wall was higher in patients with smoking-associated emphysema than in cases with AAT-deficiency emphysema (p < or = 0.05). A positive correlation between TGF-betaRII and AI was observed only in the control group (p < or = 0.005, r2 = 0.8). A negative correlation was found between the TGF-beta pathway (particularly TGF-betaRII) and T lymphocytes infiltrate in smoking-related cases (p < or = 0.05, r2 = 0.99)
  
  
  CONCLUSIONS
  Our findings suggest that apoptosis of alveolar epithelial cells plays an important role even in end-stage emphysema particularly in AAT-deficiency disease. The TGFbeta-1 pathway does not seem to directly influence epithelial turnover in end-stage disease. Inflammatory cytokine different from TGF-beta1 may differently orchestrate cell fate in AAT and smoking-related emphysema types.
authors.affiliation: Institute of Pathology, University of Padua, Italy. fiorella.calabrese@unipd.it
authors.forename: Fiorella
authors.initials: F
authors.lastname: Calabrese
authors.forename: Cinzia
authors.initials: C
authors.lastname: Giacometti
authors.forename: Bianca
authors.initials: B
authors.lastname: Beghe
authors.forename: Federico
authors.initials: F
authors.lastname: Rea
authors.forename: Monica
authors.initials: M
authors.lastname: Loy
authors.forename: Renzo
authors.initials: R
authors.lastname: Zuin
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marulli
authors.forename: Simonetta
authors.initials: S
authors.lastname: Baraldo
authors.forename: Marina
authors.initials: M
authors.lastname: Saetta
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Valente
mesh_terms: D017209:Apoptosis; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000473:pathology* / Q000503:physiopathology*; D011656:Pulmonary Emphysema / Q000473:pathology* / Q000503:physiopathology*; D020545:Respiratory Mucosa / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
chemical_list: C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1