Dislocation of E-Cadherin in the Airway Epithelium during an Antigen-Induced Asthmatic Response

Abstract

The airway epithelium plays a critical role in asthma. E-cadherin, located on the basolateral side of the epithelial cells, forms adherent junctions. To investigate the role of E-cadherin on the regulation of permeability of molecules and fluid in asthmatic responses, we observed the dynamics of E-cadherin after an immunochallenge against guinea pigs. Immunohistochemical studies revealed that E-cadherin was expressed on the lateral sides of epithelial cells before the immunochallenge and after immediate airway responses (IAR). However, E-cadherin immunoreactivities decreased from the basolateral region in late airway responses (LAR) 6 h after the challenge. Simultaneously, soluble E-cadherin immunoreactivities were detected in lavage fluid only in LAR, suggesting that E-cadherin is partly cleaved and released into the lumen in LAR. Airway permeability, which was examined by penetration of horseradish peroxidase from the airway side into the epithelium, increased in both IAR and LAR. These results suggest that E-cadherin detachment from the lateral side of the epithelial cells increased airway permeability in LAR but not IAR. We conclude that an antigen challenge causes an opening of adherent junctions as well as increases airway permeability in LAR. This mechanism would participate in airflow limitation during attacks and the increase of airway permeability and hyperresponsiveness in asthmatics.

Lysophosphatidic Acid Enhances Pulmonary Epithelial Barrier Integrity and Protects Endotoxin-induced Epithelial Barrier Disruption and Lung Injury

“…The N-terminal ectodomain of E-cadherin contains homophilic interaction specificity, and the cytoplasmic domain binds to catenins, which interact with actin (10 -13). Plasma membrane localization of E-cadherin is critical for the maintenance of epithelial cell-cell junctions and airway epithelium integrity (7,10,14). A decrease of adhesive properties of E-cadherin is related to the loss of differentiation and the subsequent acquisition of a higher motility and invasiveness of epithelial cells (10,14,15).…”

“…Plasma membrane localization of E-cadherin is critical for the maintenance of epithelial cell-cell junctions and airway epithelium integrity (7,10,14). A decrease of adhesive properties of E-cadherin is related to the loss of differentiation and the subsequent acquisition of a higher motility and invasiveness of epithelial cells (10,14,15). Dislocation or shedding of E-cadherin in the airway epithelium induces epithelial shedding and increases airway permeability in lung airway diseases (10,14,16).…”

“…A decrease of adhesive properties of E-cadherin is related to the loss of differentiation and the subsequent acquisition of a higher motility and invasiveness of epithelial cells (10,14,15). Dislocation or shedding of E-cadherin in the airway epithelium induces epithelial shedding and increases airway permeability in lung airway diseases (10,14,16). In an ovalbumin-challenged guinea pig model of asthma, it has been demonstrated that E-cadherin is dislocated from the lateral margins of epithelial cells (10).…”

“…Dislocation or shedding of E-cadherin in the airway epithelium induces epithelial shedding and increases airway permeability in lung airway diseases (10,14,16). In an ovalbumin-challenged guinea pig model of asthma, it has been demonstrated that E-cadherin is dislocated from the lateral margins of epithelial cells (10). Histamine increases airway para-cellular permeability and results in an increased susceptibility of airway epithelial cells to adenovirus infection by interrupting E-cadherin adhesion (14).…”

Le remodelage bronchique dans l’asthme : mécanismes et enjeux thérapeutiques

“…Ainsi, la surexpression de cette protéine dans des lignées de cellules épithéliales et de fibroblastes humaines bloque le cycle cellulaire et induit l'apoptose [29]. Un travail récent a montré une expression amoindrie de la E-cadhérine dans l'épithélium, associée à une libération de sa forme soluble dans le liquide de lavage broncho-alvéolaire, dans un modèle d'asthme allergique chez le cobaye [30]. Ces phénomènes s'accompagnant d'une augmentation de la perméabilité épithéliale, il a été suggéré que le clivage de la E-cadhérine, témoin d'une perte de l'intégrité épithéliale, pourrait favoriser et entretenir l'inflammation et les lésions tissulaires dans l'asthme.…”