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Neutrophil Elastase in the Pathogenesis of Chronic Obstructive Pulmonary Disease: A Review



Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality
globally. It is associated with a low quality of life and socio-economic burden. Airway destruction
in COPD pathogenesis is primarily due to the three mechanisms: protease-antiprotease imbalance,
chronic airway inflammation, and oxidative stress, which is triggered by exposure to harmful particles, such as cigarette smoking. Neutrophil elastase (NE), a serine protease stored in azurophilic
granules of neutrophils, actively participates in airway remodeling and microbiocidal activity. It hydrolyzes elastin, collagen, and other vital extracellular matrix proteins (EMP) in the respiratory tissue. In addition, neutrophil elastase activates other principal proteinases such as matrix metalloprotease (MMP)-2, MMP-9, Cathepsin B, Meprin α protease, and Calpain that amplify EMP degradation. Macrophage, the primary leukocyte, responsible for lung parenchymal inflammation in COPD,
is also activated by NE. However, neutrophil elastase level is positively correlated with the degree
of airway inflammation and disease severity. Neutrophil elastase activates reactive oxygengenerating systems such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and
myeloperoxidase and it also generates mitochondrial-derived-reactive oxygen species formation by
inducing the secretion of Interleukin (IL)-1 andTumour necrosis factor (TNF)- α. In addition, neutrophil elastase stimulates respiratory cell apoptosis by direct (e.g., activating the caspase-3 pathway) and indirect mechanisms (e.g., by secretion of Neutrophil Extracellular Traps). Surprisingly,
neutrophil elastase may have small anti-inflammatory properties. In conclusion, neutrophil elastase
is one of the main culprits responsible for COPD pathogenesis by mediating the activation of Triad
COPD pathogenesis.
