The emphysematous lung is abnormally sensitive to TRAIL-mediated apoptosisReport as inadecuate




The emphysematous lung is abnormally sensitive to TRAIL-mediated apoptosis - Download this document for free, or read online. Document in PDF available to download.

Respiratory Research

, 12:105

First Online: 01 December 2011Received: 24 March 2011Accepted: 08 August 2011

Abstract

BackgroundAlveolar apoptosis is increased in the emphysematous lung. However, mechanisms involved are not fully understood. Recently, we demonstrated that levels of TRAIL receptor 1 and 2, levels of p53, and Bax-Bcl-xL ratio were elevated in the lung of subjects with emphysema, despite smoking cessation. Thus, we postulate that due to chronic pulmonary oxidative stress, the emphysematous lung would be abnormally sensitive to TRAIL-mediated apoptosis.

MethodologyA549 cells were exposed to rTRAIL, cigarette smoke extract, and-or H2O2 prior to caspase-3 activity measurement and annexin V staining assessment. In addition, freshly resected lung samples were obtained from non-emphysematous and emphysematous subjects and exposed ex vivo to rTRAIL for up to 18 hours. Lung samples were harvested and levels of active caspase-3 and caspase-8 were measured from tissue lysates.

ResultsBoth cigarette smoke extract and H2O2 were able to sensitize A549 cells to TRAIL-mediated apoptosis. Moreover, following exposure to rTRAIL, caspase-3 and -8 were activated in lung explants from emphysematous subjects while being decreased in lung explants from non-emphysematous subjects.

Significance of the studyAlveolar sensitivity to TRAIL-mediated apoptosis is strongly increased in the emphysematous lung due to the presence of oxidative stress. This might be a new mechanism leading to increased alveolar apoptosis and persistent alveolar destruction following smoking cessation.

KeywordsApoptosis COPD oxidative stress p53 TRAIL Electronic supplementary materialThe online version of this article doi:10.1186-1465-9921-12-105 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Author: Mathieu C Morissette - Julie Parent - Julie Milot

Source: https://link.springer.com/







Related documents