Related Experiment Video
Updated: Aug 20, 2026
Monitoring Neutrophil Elastase and Cathepsin G Activity in Human Sputum Samples
Published on: May 21, 2021
Induction of human airway smooth muscle apoptosis by neutrophils and neutrophil elastase
Ute Oltmanns1, Maria B Sukkar, Shaoping Xie
1Thoracic Medicne, National Heart & Lung Institute, Imperial College, Dovehouse St., London SW3 6LY, UK.
Abstract:
Neutrophils are an important component of airway inflammation and may interact with human airway smooth muscle cells (HASMC). We investigated the effect of neutrophils and of neutrophil-derived proteases on HASMC survival. When co-incubated with neutrophils (0.1-1 x 10(6) cells/ml), attachment of human ASMC was reduced to 12.3 +/- 4.3% compared with untreated controls after 72 h. HASMC showed nuclear condensation and fragmentation (41.6 +/- 8.1% compared with baseline of 3.1 +/- 0.4%), and the biochemical markers of apoptosis, annexin V binding (9.7 +/- 0.7%; baseline 1.1 +/- 0.3%) and cleaved caspase-3 expression, were observed. The proteolytic activity released by neutrophils was essential for the proapoptotic effect because inhibition of elastase activity by alpha(1)-antitrypsin and MeOSuc-Ala-Ala-Pro-Ala-CMK (MSACK) reduced HASMC apoptosis. Human neutrophil elastase (0.1-3 microg/ml) induced apoptosis of HASMC, as well as other neutrophil serine proteases, cathepsin G, and proteinase 3. Fibronectin degradation products were present in HASMC supernatants exposed to neutrophil-conditioned media and to neutrophil elastase. The local release of proteases from neutrophils present in airway smooth muscle cells may lead to HASMC apoptosis as a result of matrix degradation and loss of cell attachment. This may limit pathologic changes such as ASMC hyperplasia and extracellular matrix deposition seen in airway remodeling.
Insights
Neutrophils induce apoptosis in human airway smooth muscle cells (HASMC) via protease release, leading to reduced cell attachment and matrix degradation. This mechanism may influence airway remodeling in inflammatory conditions.
Area of Science:
- Cell Biology
- Immunology
- Respiratory Medicine
Background:
- Neutrophils are key inflammatory cells in airways.
- Neutrophil interactions with human airway smooth muscle cells (HASMC) are not fully understood.
- Airway remodeling involves changes in HASMC.
Purpose of the Study:
- To investigate the impact of neutrophils and their proteases on HASMC survival.
- To determine if neutrophil proteases induce apoptosis in HASMC.
- To explore the role of HASMC apoptosis in airway remodeling.
Main Methods:
- Co-incubation of HASMC with neutrophils.
- Assessment of HASMC attachment, nuclear morphology, and apoptosis markers (annexin V, cleaved caspase-3).
- Inhibition of neutrophil elastase activity and assessment of its effect on HASMC apoptosis.
- Analysis of fibronectin degradation products.
Main Results:
- Neutrophil co-incubation significantly reduced HASMC attachment and induced apoptosis.
- Neutrophil proteases, including human neutrophil elastase, cathepsin G, and proteinase 3, were responsible for HASMC apoptosis.
- Inhibiting elastase activity attenuated HASMC apoptosis.
- Degradation of fibronectin was observed in HASMC exposed to neutrophil-derived proteases.
Conclusions:
- Neutrophil-derived proteases induce HASMC apoptosis through matrix degradation and loss of cell attachment.
- This process may play a role in limiting airway remodeling, such as smooth muscle hyperplasia and extracellular matrix deposition.
- Understanding this interaction is crucial for managing airway inflammation and remodeling.
Related Concept Videos
01:17The Extrinsic Apoptotic Pathway
01:30Apoptosis