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Current Respiratory Medicine Reviews


ISSN (Print): 1573-398X
ISSN (Online): 1875-6387

Review Article

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

Author(s): Pandit Bagus Tri Saputra, Dinda Dwi Purwati, Alyaa Ulaa Dhiya Ulhaq, Sherly Yolanda, Yovita Citra Eka Dewi Djatioetomo, Alfian Nur Rosyid* and Arief Bakhtiar

Volume 19, Issue 1, 2023

Published on: 10 November, 2022

Page: [29 - 35] Pages: 7

DOI: 10.2174/1573398X18666220929170117

Price: $65


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 and Tumour 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.

Keywords: COPD, neutrophil elastase, pathogenesis, pulmonary disease, chronic respiratory disease, extracellular matrix proteins (EMP).

Graphical Abstract
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