Contact Activation via ICAM-1 Induces Changes in Airway Epithelial Permeability in vitro

The role of ICAM-1 in contact activation of the bronchial epithelial cells is elucidated. Direct contact between epithelial cells and leukocytes is required to change transepithelial electrical resistance (TER) of the epithelium. Migration of human neutrophils across the layers of cultured human airway epithelial cells (Calu-3) or primary cow tracheal epithelial cells was induced by an fMLP gradient. Migrating neutrophils decreased TER and increased permeability to albumin. Monoclonal antibodies to ICAM-1 reduced neutrophil migration, thus reducing the changes in TER and changes in the epithelial permeability to albumin. By confocal microscopy, ERK1/2 was found to be locally activated in the epithelial cells at the sites of migration and cross-linking of ICAM-1. Blockade of ERK1/2 by PD98059 decreased the changes in TER which were induced by ICAM-1 cross-linking. Contact activation of the bronchial epithelial cells, involving ICAM-1 via local activation of ERK1/2, is an important mechanism of alteration of the bronchial epithelial permeability.