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Myeloperoxidase impairs mucociliary transport on human airway epithelium

Allison Boboltz1, Vaidehi Rathi1, Sahana Kumar1,2

  • 1Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.

Disease Models & Mechanisms
|May 1, 2026
PubMed

Insights

Myeloperoxidase (MPO) impairs airway clearance in cystic fibrosis (CF) by inhibiting mucociliary transport. N-acetyl cysteine can reverse this MPO-induced dysfunction, suggesting MPO as a therapeutic target.

Area of Science:

  • Pulmonary Medicine
  • Cell Biology
  • Biochemistry

Background:

  • Neutrophil-driven inflammation is a key challenge in cystic fibrosis (CF) lung disease.
  • Myeloperoxidase (MPO), a neutrophilic enzyme, is concentrated in CF airways and linked to mucus plugging.
  • MPO's role in impairing mucociliary transport, a critical airway clearance mechanism, is not fully understood.

Purpose of the Study:

  • To investigate the impact of MPO on human airway epithelial cell function.
  • To assess MPO's effect on barrier integrity, mucin production, mucus viscoelasticity, and mucociliary transport.
  • To evaluate MPO's activity under both healthy and CF-like ionic conditions.

Main Methods:

  • Utilized fully differentiated human airway epithelial cell cultures.
  • Employed live cell imaging and particle velocimetry to measure mucociliary transport.
  • Assessed MPO's effects at ionic conditions mimicking healthy and CF airways.

Main Results:

  • MPO significantly inhibits mucociliary transport in vitro under both healthy and CF-like conditions.
  • MPO's impairment of mucus clearance was comparable to that of neutrophil elastase (NE).
  • N-acetyl cysteine treatment reversed MPO-mediated mucociliary dysfunction by cleaving disulfide bonds.

Conclusions:

  • Myeloperoxidase (MPO) directly impairs mucociliary transport and airway clearance in CF.
  • MPO represents a potential therapeutic target for muco-obstructive lung diseases.
  • N-acetyl cysteine demonstrates potential in mitigating MPO-induced airway dysfunction.
Keywords:
Airway clearanceMucolyticsMucusMyeloperoxidase

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