Figure 3

Interaction of apoptosis with other pathogenetic mechanisms in COPD, including inflammation, oxidative stress and protease/anti-proteinase imbalance. 1. Neutrophil elastase (NE) cleaves the phosphatidylserine receptor on macrophages, resulting in impaired clearance of apoptotic cells and sustained inflammation [54]. 2. Cytotoxic CD8+ T-cells cause apoptosis of alveolar epithelial cells through the release of perforins and granzyme-B [57,58]. 3. Degradation of the basement membrane (BM) by matrix metalloproteinases (MMPs) leads to loss of survival signals and induces apoptosis of epithelial cells [60]. 4. Apoptosis may also be affected by direct proteolysis of death-inducing signals. It has been shown that MMP-7 sheds and activates Fas ligand (FasL) that is produced by epithelial cells, thereby mediating apoptosis [62]. 5. Oxidative stress could lead to a reduction of Vascular Endothelial Growth Factor (VEGF) levels, resulting in apoptosis of alveolar endothelial cells [29]. NE: neutrophil elastase; BM: basement membrane; MMPs: matrix metalloproteinases; TIMP: tissue inhibitor of metalloproteinase; α1-AT: α1-anti-trypsin; FasL: Fas ligand; VEGF: vascular endothelial growth factor.