| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
1 Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, NC, USA
* To whom correspondence should be addressed. E-mail: ray_caldwell{at}med.unc.edu.
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 epithelial-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-/
) increased Na+-transport ~2-fold. 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 
-, -, and -ENaC subunits. However, no enzyme effects were observed on basally active ENaCs. Trypsin exposure following hNE revealed no additional increase in amiloridesensitive 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.
This article has been cited by other articles:
|
|
 |
|
  P. Svenningsen, T. R. Uhrenholt, Y. Palarasah, K. Skjodt, B. L. Jensen, and O. Skott Prostasin-dependent activation of epithelial Na+ channels by low plasmin concentrations Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2009; 297(6): R1733 - R1741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Haerteis, B. Krueger, C. Korbmacher, and R. Rauh The {delta}-Subunit of the Epithelial Sodium Channel (ENaC) Enhances Channel Activity and Alters Proteolytic ENaC Activation J. Biol. Chem., October 16, 2009; 284(42): 29024 - 29040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Garcia-Caballero, J. E. Rasmussen, E. Gaillard, M. J. Watson, J. C. Olsen, S. H. Donaldson, M. J. Stutts, and R. Tarran SPLUNC1 regulates airway surface liquid volume by protecting ENaC from proteolytic cleavage PNAS, July 7, 2009; 106(27): 11412 - 11417. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Swystun, B. Renaux, F. Moreau, S. Wen, M. A. Peplowski, M. D. Hollenberg, and W. K. MacNaughton Serine proteases decrease intestinal epithelial ion permeability by activation of protein kinase C{zeta} Am J Physiol Gastrointest Liver Physiol, July 1, 2009; 297(1): G60 - G70. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Coote, H. C. Atherton-Watson, R. Sugar, A. Young, A. MacKenzie-Beevor, M. Gosling, G. Bhalay, G. Bloomfield, A. Dunstan, R. J. Bridges, et al. Camostat Attenuates Airway Epithelial Sodium Channel Function in Vivo through the Inhibition of a Channel-Activating Protease J. Pharmacol. Exp. Ther., May 1, 2009; 329(2): 764 - 774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Svenningsen, C. Bistrup, U. G. Friis, M. Bertog, S. Haerteis, B. Krueger, J. Stubbe, O. N. Jensen, H. C. Thiesson, T. R. Uhrenholt, et al. Plasmin in Nephrotic Urine Activates the Epithelial Sodium Channel J. Am. Soc. Nephrol., February 1, 2009; 20(2): 299 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Butterworth, R. S. Edinger, R. A. Frizzell, and J. P. Johnson Regulation of the epithelial sodium channel by membrane trafficking Am J Physiol Renal Physiol, January 1, 2009; 296(1): F10 - F24. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Garcia-Caballero, Y. Dang, H. He, and M. J. Stutts ENaC Proteolytic Regulation by Channel-activating Protease 2 J. Gen. Physiol., October 27, 2008; 132(5): 521 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Tarran Raising the volume on near-silent epithelial Na+ channels J. Physiol., October 1, 2008; 586(19): 4583 - 4584. [Full Text] [PDF]
|
|
|
|
|
|
V. Nesterov, A. Dahlmann, M. Bertog, and C. Korbmacher Trypsin can activate the epithelial sodium channel (ENaC) in microdissected mouse distal nephron Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1052 - F1062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Diakov, K. Bera, M. Mokrushina, B. Krueger, and C. Korbmacher Cleavage in the {gamma}-subunit of the epithelial sodium channel (ENaC) plays an important role in the proteolytic activation of near-silent channels J. Physiol., October 1, 2008; 586(19): 4587 - 4608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Carattino, R. P. Hughey, and T. R. Kleyman Proteolytic Processing of the Epithelial Sodium Channel {gamma} Subunit Has a Dominant Role in Channel Activation J. Biol. Chem., September 12, 2008; 283(37): 25290 - 25295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Frindt, Z. Ergonul, and L. G. Palmer Surface Expression of Epithelial Na Channel Protein in Rat Kidney J. Gen. Physiol., June 1, 2008; 131(6): 617 - 627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Myerburg, E. E. McKenna, C. J. Luke, R. A. Frizzell, T. R. Kleyman, and J. M. Pilewski Prostasin expression is regulated by airway surface liquid volume and is increased in cystic fibrosis Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L932 - L941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Hirsh, J. Zhang, A. Zamurs, J. Fleegle, W. R. Thelin, R. A. Caldwell, J. R. Sabater, W. M. Abraham, M. Donowitz, B. Cha, et al. Pharmacological Properties of N-(3,5-Diamino-6-chloropyrazine-2-carbonyl)-N'-4-[4-(2,3-dihydroxypropoxy)phenyl]butyl-guanidine Methanesulfonate (552-02), a Novel Epithelial Sodium Channel Blocker with Potential Clinical Efficacy for Cystic Fibrosis Lung Disease J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 77 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Wall and L. P. McCluskey Rapid Changes in Gustatory Function Induced by Contralateral Nerve Injury and Sodium Depletion Chem Senses, February 1, 2008; 33(2): 125 - 135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Adebamiro, Y. Cheng, U. S. Rao, H. Danahay, and R. J. Bridges A Segment of {gamma} ENaC Mediates Elastase Activation of Na+ Transport J. Gen. Physiol., November 26, 2007; 130(6): 611 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Scuri, J. R. Sabater, and W. M. Abraham Hyaluronan blocks porcine pancreatic elastase-induced mucociliary dysfunction in allergic sheep J Appl Physiol, June 1, 2007; 102(6): 2324 - 2331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Morimoto, W. Liu, C. Woda, M. D. Carattino, Y. Wei, R. P. Hughey, G. Apodaca, L. M. Satlin, and T. R. Kleyman Mechanism underlying flow stimulation of sodium absorption in the mammalian collecting duct Am J Physiol Renal Physiol, September 1, 2006; 291(3): F663 - F669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sheng, M. D. Carattino, J. B. Bruns, R. P. Hughey, and T. R. Kleyman Furin cleavage activates the epithelial Na+ channel by relieving Na+ self-inhibition Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1488 - F1496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Andreasen, G. Vuagniaux, N. Fowler-Jaeger, E. Hummler, and B. C. Rossier Activation of Epithelial Sodium Channels by Mouse Channel Activating Proteases (mCAP) Expressed in Xenopus Oocytes Requires Catalytic Activity of mCAP3 and mCAP2 but not mCAP1 J. Am. Soc. Nephrol., April 1, 2006; 17(4): 968 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Serisier, J. K. Shute, P. M. Hockey, B. Higgins, J. Conway, and M. P. Carroll Inhaled heparin in cystic fibrosis Eur. Respir. J., February 1, 2006; 27(2): 354 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Sabater, T. A. Lee, and W. M. Abraham Comparative Effects of Salmeterol, Albuterol, and Ipratropium on Normal and Impaired Mucociliary Function in Sheep Chest, November 1, 2005; 128(5): 3743 - 3749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Lee, R. C. Rancourt, G. del Val, K. Pack, C. Pardee, F. J. Accurso, and C. W. White Thioredoxin and dihydrolipoic acid inhibit elastase activity in cystic fibrosis sputum Am J Physiol Lung Cell Mol Physiol, November 1, 2005; 289(5): L875 - L882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Loffing and L. Schild Functional Domains of the Epithelial Sodium Channel J. Am. Soc. Nephrol., November 1, 2005; 16(11): 3175 - 3181. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Moody, C. Pennington, C. Schultz, R. Caldwell, C. Dinkel, M. W. Rossi, S. McNamara, J. Widdicombe, S. Gabriel, and A. E. Traynor-Kaplan Inositol polyphosphate derivative inhibits Na+ transport and improves fluid dynamics in cystic fibrosis airway epithelia Am J Physiol Cell Physiol, September 1, 2005; 289(3): C512 - C520. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
