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

Pandit Bagus Tri Saputra, Dinda Dwi Purwati, Alyaa Ulaa Dhiya Ulhaq, Sherly Yolanda, Yovita Citra Eka Dewi Djatioetomo, Alfian Nur Rosyid, Arief Bakhtiar

Research output: Contribution to journalReview articlepeer-review

3 Citations (Scopus)

Abstract

Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of mortali-ty 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 imbal-ance, 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 az-urophilic granules of neutrophils, actively participates in airway remodeling and microbiocidal ac-tivity. 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 oxygen-generating 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 path-way) 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.

Original languageEnglish
Pages (from-to)29-35
Number of pages7
JournalCurrent Respiratory Medicine Reviews
Volume19
Issue number1
DOIs
Publication statusPublished - 2023

Keywords

  • COPD
  • chronic respiratory disease
  • extracellular matrix proteins (EMP)
  • neutrophil elastase
  • pathogenesis
  • pulmonary disease

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