Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema.
Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation of the airways and progressive destruction of lung parenchyma, a process that in most cases is initiated by cigarette smoking. Several mechanisms are involved in the development of the disease: influx of inflammatory cells into the lung (leading to chronic inflammation of the airways), imbalance between proteolytic and anti-proteolytic activity (resulting in the destruction of healthy lung tissue) and oxidative stress. Recently, an increasing number of data suggest a fourth important mechanism involved in the development of COPD: apoptosis of structural cells in the lung might possibly be an important upstream event in the pathogenesis of COPD. There is an increase in apoptotic alveolar epithelial and endothelial cells in the lungs of COPD patients. Since this is not counterbalanced by an increase in proliferation of these structural cells, the net result is destruction of lung tissue and the development of emphysema. Data from animal models suggest a role for Vascular Endothelial Growth Factor (VEGF) in the induction of apoptosis of structural cells in the lung. Other mediators of apoptosis, such as caspase-3 and ceramide, could be interesting targets to prevent apoptosis and the development of emphysema. In this review, recent data on the role of apoptosis in COPD from both animal models as well as from studies on human subjects will be discussed. The aim is to provide an up to date summary on the increasing knowledge on the role of apoptosis in COPD and pulmonary emphysema.
Demedts
Ingel K
IK
Department of Respiratory Diseases, Ghent University Hospital, Belgium. M.DemedtsIngelK@UGent.be
Demoor
Tine
T
Bracke
Ken R
KR
Joos
Guy F
GF
Brusselle
Guy G
GG
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000502:physiology; D049109:Cell Proliferation; D002518:Ceramides / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D004727:Endothelium / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018384:Oxidative Stress / Q000502:physiology; D010447:Peptide Hydrolases / Q000502:physiology; D011014:Pneumonia / Q000473:pathology / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D011656:Pulmonary Emphysema / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D020545:Respiratory Mucosa / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D012907:Smoking / Q000009:adverse effects; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D002518:Ceramides; D042461:Vascular Endothelial Growth Factor A; D010447:Peptide Hydrolases; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases