TY - JOUR
T1 - Neutrophil Elastase in the Pathogenesis of Chronic Obstructive Pulmonary Disease
T2 - A Review
AU - Saputra, Pandit Bagus Tri
AU - Purwati, Dinda Dwi
AU - Ulhaq, Alyaa Ulaa Dhiya
AU - Yolanda, Sherly
AU - Djatioetomo, Yovita Citra Eka Dewi
AU - Rosyid, Alfian Nur
AU - Bakhtiar, Arief
N1 - Publisher Copyright:
© 2023 Bentham Science Publishers.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - COPD
KW - chronic respiratory disease
KW - extracellular matrix proteins (EMP)
KW - neutrophil elastase
KW - pathogenesis
KW - pulmonary disease
UR - http://www.scopus.com/inward/record.url?scp=85150711824&partnerID=8YFLogxK
U2 - 10.2174/1573398X18666220929170117
DO - 10.2174/1573398X18666220929170117
M3 - Review article
AN - SCOPUS:85150711824
SN - 1573-398X
VL - 19
SP - 29
EP - 35
JO - Current Respiratory Medicine Reviews
JF - Current Respiratory Medicine Reviews
IS - 1
ER -