The surface epithelium of the airway mucosa forms a continuous barrier to a wide number of noxious substances present in the lumen. The restoration of the barrier integrity after injury represents a key issue in the defense capacity of the airway epithelium. Using an in vitro
wound repair model of the airway epithelium, we investigated the dynamic of the restoration of the epithelial barrier integrity during the
wound repair process. Airway epithelial cells in culture were chemically wounded by
sodium hydroxide. The immunolocalization of zonula occludens 1 (ZO-1), a cytoplasmic
protein associated with the tight junctions, was examined during the
wound repair process. Junctional integrity was examined by analyzing the transepithelial resistance (TER) and the permeability to [3H]
mannitol and by visualizing the permeability to
lanthanum nitrate during 5 days after injury. Immediately after injury, we simultaneously observed a 36.7% decrease in the TER and a 74.9% rise in the permeability to [3H]
mannitol. In addition,
lanthanum nitrate penetrated in the intercellular spaces in the repairing areas, which was also characterized by the absence of ZO-1 staining, as opposed to nonrepairing cells. TER and [3H]
mannitol flux values as well as
lanthanum nitrate and ZO-1 localizations were found to be similar to those observed in confluent cultures only 1 to 2 days after complete
wound closure. This study demonstrates that using our culture model, confluent airway epithelial cells form a continuous and efficient barrier with tight junctions. Epithelial integrity is affected immediately after injury and is completely restored within 1 to 2 days after
wound closure. During such a period of time, the airway epithelium may remain exposed to the noxious effect of environment in vivo, which can prevent the epithelial barrier restoration by modifying tight junction formation.