{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:12:37Z","timestamp":1791022357660,"version":"4.1.0"},"reference-count":39,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2005,5]]},"abstract":"<jats:p>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<jats:sup>+<\/jats:sup>absorption and consequent depletion of the airway surface liquid layer. Although endogenous epithelium-derived serine proteases regulate epithelial Na<jats:sup>+<\/jats:sup>transport, the effects of neutrophil elastase on epithelial Na<jats:sup>+<\/jats:sup>transport and epithelial Na<jats:sup>+<\/jats:sup>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-\/\u03b2\u03b3) increased Na<jats:sup>+<\/jats:sup>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<jats:sup>+<\/jats:sup>transport. At the level of the single channel, submicromolar concentrations of hNE increased activity of near-silent ENaC \u223c108-fold in patches from NIH-3T3 cells expressing rat \u03b1-, \u03b2-, and \u03b3-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<jats:sup>+<\/jats:sup>transport, likely through proteolytic activation of ENaC. The hNE-induced increase of near-silent ENaC activity in CF airways could contribute to Na<jats:sup>+<\/jats:sup>hyperabsorption, reduced airway surface liquid height, and dehydrated mucus culminating in inefficient mucociliary clearance.<\/jats:p>","DOI":"10.1152\/ajplung.00435.2004","type":"journal-article","created":{"date-parts":[[2005,1,8]],"date-time":"2005-01-08T01:38:17Z","timestamp":1105148297000},"page":"L813-L819","source":"Crossref","is-referenced-by-count":199,"title":["Neutrophil elastase activates near-silent epithelial Na<sup>+<\/sup>channels and increases airway epithelial Na<sup>+<\/sup>transport"],"prefix":"10.1152","volume":"288","author":[{"given":"Ray A.","family":"Caldwell","sequence":"first","affiliation":[{"name":"The Cystic Fibrosis\/Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Boucher","sequence":"additional","affiliation":[{"name":"The Cystic Fibrosis\/Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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