Neutrophil elastase activates near-silent epithelial Na+ channels and increases airway epithelial Na+ transport
Year: 2025
Type: article
Abstract: Neutrophil elastase is a serine protease that is abundant in the airways of individuals with cystic fibrosis (CF), a genetic disease manifested by excessive airway Na+ absorption and consequent depletion of the airway surface liquid layer. Although endogenous epithelium-derived serine proteases regulate epithelial Na+ transport, the effects of neutrophil elastase on epithelial Na+ transport and epithelial Na+ channel (ENaC) activity are unknown. Low micromolar concentrations of human neutrophil elastase (hNE) applied to the apical surface of a human bronchial cell line (16HBE14o-/βγ) increased Na + transport about twofold. Similar effects were observed with trypsin, also a serine protease. Proteolytic inhibitors of hNE or trypsin selectively abolished the enzyme-induced increase of epithelial Na+ transport. At the level of the single channel, submicromolar concentrations of hNE increased activity of near-silent ENaC ∼108-fold in patches from NIH-3T3 cells expressing rat α-, β-, and γ-ENaC subunits. However, no enzyme effects were observed on basally active ENaCs. Trypsin exposure following hNE revealed no additional increase in amiloride-sensitive short-circuit current or in ENaC activity, suggesting these enzymes share a common mode of action for increasing Na+ transport, likely through proteolytic activation of ENaC. The hNE-induced increase of near-silent ENaC activity in CF airways could contribute to Na+ hyperabsorption, reduced airway surface liquid height, and dehydrated mucus culminating in inefficient mucociliary clearance.
DOI: 10.17615/k51x-c631
Authors: Boucher R.C., Caldwell R.A., Stutts M.J.
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4416236897
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