What question did this study set out to answer?

The research aims to evaluate the influence of activated neutrophil proteases on small airway function.

March 18, 2026

Effect of human neutrophil proteases on ex vivo small airway function

Key Points

The research aims to evaluate the influence of activated neutrophil proteases on small airway function.
Used precision-cut lung slices (PCLS) from rats to assess airway function.
Incubated PCLS in supernatants from fMLP-stimulated neutrophils from non-smokers, smokers, and COPD patients.
Measured contraction levels in response to carbachol (CCh) and analyzed airway reopening after washout.
Quantified levels of neutrophil elastase (NE), MMP-8, MMP-9, and myeloperoxidase (MPO) in supernatants.
Maximal airway contraction was significantly reduced in supernatants from neutrophils compared to untreated samples.
Airway reopening was significantly enhanced in samples incubated with neutrophil supernatants.
A notable decrease in baseline airway patency was observed in airways incubated with COPD neutrophil supernatants.
Maximal contraction negatively correlated with levels of neutrophil elastase and active MMP-9.

Abstract

Small airways are the main site of airflow obstruction in COPD. Neutrophils are implicated in COPD pathophysiology via the activity of their released products, including proteases, which damage airway tissue. We studied the effects of activated neutrophil supernatants on small airway function in rat precision-cut lung slices (PCLS) using videomicroscopy. PCLS were incubated overnight in fMLP-stimulated neutrophil supernatants from non-smokers (NS), smokers (S) and COPD patients (C), and contraction to carbachol (CCh) assessed. Supernatant levels of MMP-8, -9, neutrophil elastase (NE) and myeloperoxidase (MPO) were measured. Compared with untreated (UT) airways, airway maximal contraction (at 10µM CCh) was significantly reduced after incubation in supernatants (UT 80±4; NS 56±10; S 40±11; C 52±7%, n=6-10, p<0.01). Airway reopening after CCh washout was significantly augmented in airways incubated in neutrophil supernatants, compared with UT airways (UT 18±8; NS 157±25; S 186±68; C 171±79% difference in contraction (10µM CCh vs. post-washout), n=4, p<0.05). There was a significant decrease in baseline airway patency after incubation in COPD neutrophil supernatants, compared with UT airways (10±5 vs . 40±7% decrease in patency, n=8-10, p<0.01). Maximal contraction correlated with supernatant NE (r=-0.5, n=46, p<0.001) and active MMP-9 (r=-0.6, n=27, p<0.001), whilst airway reopening correlated with NE (r=0.6, n=11). Hence, activated neutrophil supernatants reduce maximal contraction, augment reopening, and decrease baseline patency of small airways, possibly due to proteolytic action. Thus, increased numbers of neutrophils in COPD may contribute to the airway dysfunction characteristic of the disease.

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