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Calabrese, Fiorella and Giacometti, Cinzia and Beghe, Bianca and Rea , Federico and Loy, Monica and Zuin, Renzo and Marulli, Giuseppe and Baraldo, Simonetta and Saetta, Marina and Valente, Marialuisa (2005) Marked alveolar apoptosis/proliferation imbalance in end-stage emphysema. [Online journal papers]

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Per gentile concessione di: http://respiratory-research.com/content/6/1/14

Abstract (english)

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 α1antitrypsin (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)-β1 pathway was
also investigated and correlated with epithelial cell turnover and with the severity of inflammatory cell
Results: The apoptotic index (AI) was significantly higher in emphysematous lungs compared to the
control group (p ≤ 0.01), particularly if only lungs with AAT-deficiency emphysema were considered (p ≤
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
≤ 0.05). TGF-β1 expression in the alveolar wall was higher in patients with smoking-associated emphysema
than in cases with AAT-deficiency emphysema (p ≤ 0.05). A positive correlation between TGF-βRII and AI
was observed only in the control group (p ≤ 0.005, r2 = 0.8). A negative correlation was found between
the TGF-β pathway (particularly TGF-βRII) and T lymphocytes infiltrate in smoking-related cases (p ≤ 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 TGFβ-1 pathway does not seem to
directly influence epithelial turnover in end-stage disease. Inflammatory cytokine different from TGF-β1
may differently orchestrate cell fate in AAT and smoking-related emphysema types.

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EPrint type:Online journal papers
Anno di Pubblicazione:2005
Key Words:emphysema, Apoptosis
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/10 Malattie dell'apparato respiratorio
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze Cardiologiche, Toraciche e Vascolari
Dipartimenti > pre 2012 - Dipartimento di Medicina Clinica e Sperimentale
Dipartimenti > pre 2012 - Dipartimento di Scienze Medico Diagnostiche e Terapie Speciali
Codice ID:1268
Depositato il:09 Dec 2008
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