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-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.
Goto
Y
Y
Department of Pulmonary Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
Uchida
Y
Y
Nomura
A
A
Sakamoto
T
T
Ishii
Y
Y
Morishima
Y
Y
Masuyama
K
K
Sekizawa
K
K
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D007507:Therapeutic Irrigation; D013997:Time Factors; D014132:Trachea / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure
D015820:Cadherins; D012333:RNA, Messenger; D010047:Ovalbumin