HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/4/L628    most recent 00046.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Winter, M. C. Articles by Shasby, D. M. Search for Related Content PubMed PubMed Citation Articles by Winter, M. C. Articles by Shasby, D. M.

PAR2 activation interrupts E-cadherin adhesion and compromises the airway epithelial barrier: protective effect of -agonists

Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa

Submitted 8 February 2006 ; accepted in final form 11 May 2006

The airway epithelium is an important barrier between the environment and subepithelial tissues. The epithelium is also divided into functionally restricted apical and basolateral domains, and this restriction is dependent on the elements of the barrier. The protease-activated receptor-2 (PAR2) receptor is expressed in airway epithelium, and its activation initiates multiple effects including enhanced airway inflammation and reactivity. We hypothesized that activation of PAR2 would interrupt E-cadherin adhesion and compromise the airway epithelial barrier. The PAR2-activating peptide (PAR2-AP, SLIGRL) caused an immediate 50% decrease in the transepithelial resistance of primary human airway epithelium that persisted for 6–10 min. The decrease in resistance was accompanied by an increase in mannitol flux across the epithelium and occurred in cystic fibrosis transmembrane conductance receptor (CFTR) epithelium pretreated with amiloride to block Na and Cl conductances, confirming that the decrease in resistance represented an increase in paracellular conductance. In parallel experiments, activation of PAR2 interrupted the adhesion of E-cadherin-expressing L cells and of primary airway epithelial cells to an immobilized E-cadherin extracellular domain, confirming the hypothesis that activation of PAR2 interrupts E-cadherin adhesion. Selective interruption of E-cadherin adhesion with antibody to E-cadherin decreased the transepithelial resistance of primary airway epithelium by >80%. Pretreatment of airway epithelium or the E-cadherin-expressing L cells with the long-acting -agonist salmeterol prevented PAR2 activation from interrupting E-cadherin adhesion and compromising the airway epithelial barrier. Activation of PAR2 interrupts E-cadherin adhesion and compromises the airway epithelial barrier.

protease-activated receptor; histamine; barrier function

This article has been cited by other articles:

				M. C. Winter, S. S. Shasby, and D. M. Shasby PAR2 Interrupts E-Cadherin Adhesion and Decreases the Transepithelial Resistance of Epithelia by Phosphorylating Tyrosines 489 and 654 of Beta-Catenin Proceedings of the ATS, April 15, 2008; 5(3): 359 - 359. [Full Text] [PDF]

				M. C. Winter, S. Shasby, and D. M. Shasby Compromised E-cadherin adhesion and epithelial barrier function with activation of G protein-coupled receptors is rescued by Y-to-F mutations in {beta}-catenin Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L442 - L448. [Abstract] [Full Text] [PDF]

				T. Stevens Epithelium: sticking it out, together Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L440 - L441. [Full Text] [PDF]

				E. Ostrowska, E. Sokolova, and G. Reiser PAR-2 activation and LPS synergistically enhance inflammatory signaling in airway epithelial cells by raising PAR expression level and interleukin-8 release Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1208 - L1218. [Abstract] [Full Text] [PDF]

				D. M. Shasby Cell-cell adhesion in lung endothelium Am J Physiol Lung Cell Mol Physiol, March 1, 2007; 292(3): L593 - L607. [Abstract] [Full Text] [PDF]