Dislocation of E-cadherin in the airway epithelium during an antigen-induced asthmatic response

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-c adherin after an immunochallenge against guinea pigs. Immunohistochemical s tudies revealed that E-cadherin was expressed on the lateral sides of epith elial cells before the immunochallenge and after immediate airway responses (IAR). However, E-cadherin immunoreactivities decreased from the basolater al region in late airway responses (LAR) 6 h after the challenge. Simultane ously, 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 o f horseradish peroxidase from the airway side into the epithelium, increase d in both IAR and LAR, These results suggest that E-cadherin detachment fro m the lateral side of the epithelial cells increased airway permeability in LAR but not IAR. We conclude that an antigen challenge causes an opening o f adherent junctions as well as increases airway permeability in LAR. This mechanism would participate in airflow limitation during attacks and the in crease of airway permeability and hyperresponsiveness in asthmatics.