PAR2 activation interrupts E-cadherin adhesion and compromises the airway epithelial barrier: protective effect of β-agonists
| Autor: | Michael C. Winter, Sandra S. Shasby, D. Michael Shasby, Dana R. Ries |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Pulmonary and Respiratory Medicine
Pathology medicine.medical_specialty Physiology Bronchi In Vitro Techniques Biology Permeability chemistry.chemical_compound Physiology (medical) Cell Adhesion Cyclic AMP Electric Impedance medicine Humans Receptor PAR-2 Albuterol Protease-activated receptor Receptors Histamine H1 Receptor Salmeterol Xinafoate Cells Cultured Barrier function Cadherin Epithelial Cells Cell Biology Adhesion Adrenergic beta-Agonists Thionucleotides respiratory system Cadherins Epithelium respiratory tract diseases Cell biology medicine.anatomical_structure chemistry Respiratory epithelium Histamine |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 291:L628-L635 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00046.2006 |
| Popis: | 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 β-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. |
| Databáze: | OpenAIRE |
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