Protease–antiprotease imbalance (e.g. activation of MMPs, such as MMP-9 and -12, activation of serine proteases, such as neutrophil elastase, and inactivation of α1-antitrypsin) |
Activation of CD8+ T-cells to release perforin and granzymes |
Injurious apoptosis of alveolar cells (e.g. decrease in signalling by VEGF, which stimulates endothelial and alveolar growth and survival) |
Increased lung ageing and senescence leading to a failure of lung maintenance and repair (e.g. cigarette smoke inhibits alveolar repair) |
Ineffective clearance of apoptotic cells by macrophages leading to decrease in anti-inflammatory or anti-immunological mechanisms |
Mitochondrial dysfunction, with increase in oxidative stress leading to increased apoptosis of cells (e.g. through SIRT-1) |
MMP: matrix metalloproteinase; VEGF: vascular endothelial growth factor; SIRT: nicotinamide adenine dinucleotide-dependent deacetylase sirtuin.