Marked alveolar apoptosis/proliferation imbalance in end-stage emphysema

Calabrese Fiorella, Giacometti Cinzia, Beghe Bianca, Rea Federico, Loy Monica, Zuin Renzo, Marulli Giuseppe, Baraldo Simonetta, Saetta Marina, Valente, Valente Marialuisa

Description

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 infiltrate. 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, r 2 = 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, r 2 = 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.

Sujets

• Apoptosis
• Prolifération

Informations

• Publié par: biomed
• Publié le: 01 janvier 2005
• Nombre de lectures: 9
• Langue: English

Extrait

Respiratory Research

BioMedCentral

Open Access Research Marked alveolar apoptosis/proliferation imbalance in end-stage emphysema 1 †1†2 †3 Fiorella Calabrese*, Cinzia Giacometti, Bianca Beghe, Federico Rea, †3 †2†3 †2 Monica Loy, Renzo Zuin, Giuseppe Marulli, Simonetta Baraldo, †2 †1 Marina Saettaand Marialuisa Valente

1 2 Address: Instituteof Pathology, University of Padua, Italy,Department of Clinical and Experimental Medicine, Section of Respiratory Diseases, 3 University of Padua, Italy andDepartment of Gastroenterological Sciences, Section of Thoracic Surgery, University of Padua, Italy Email: Fiorella Calabrese*  [e-mail]; Cinzia Giacometti  [e-mail]; Bianca Beghe  [e-mail]; Federico Rea  [e-mail]; Monica Loy  [e-mail]; Renzo Zuin  [e-mail]; Giuseppe Marulli  [e-mail]; Simonetta Baraldo  [e-mail]; Marina Saetta  [e-mail]; Marialuisa Valente  [e-mail] * Corresponding author†Equal contributors

Published: 10 February 2005Received: 29 July 2004 Accepted: 10 February 2005 Respiratory Research2005,6:14 doi:10.1186/1465-9921-6-14 This article is available from: http://respiratory-research.com/content/6/1/14 © 2005 Calabrese et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

apoptosisproliferationend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 7α1antitrypsin (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 infiltrate. 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 2 was observed only in the control group (p≤= 0.8). A negative correlation was found between0.005, r the TGF-βpathway (particularly TGF-βRII) and T lymphocytes infiltrate in smoking-related cases (p≤0.05, 2 r =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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