Marked alveolar apoptosis/proliferation imbalance in end-stage emphysema

Respir Res. 2005 Feb 10;6(1):14. doi: 10.1186/1465-9921-6-14.


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)

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Cell Proliferation
  • Female
  • Humans
  • In Vitro Techniques
  • Lung Transplantation
  • Male
  • Middle Aged
  • Pulmonary Alveoli / pathology*
  • Pulmonary Alveoli / physiopathology*
  • Pulmonary Emphysema / pathology*
  • Pulmonary Emphysema / physiopathology*
  • Respiratory Mucosa / pathology
  • Respiratory Mucosa / physiopathology
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta1


  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1