PROMPT EPITHELIAL DAMAGE AND RESTITUTION PROCESSES IN ALLERGEN CHALLENGED GUINEA-PIG TRACHEA IN-VIVO

Background Little is known about the induction and the morphology of e pithelial damage, and of the ensuing epithelial restitution processes in allergic airways. Objective To examine epithelial damage and restit ution in allergen challenged guinea-pig trachea. Methods Whole-mount t echniques, transmission and scanning electron microscopy, cryosectioni ng, and histochemical staining were used. Cell proliferation was monit ored by BrdU-immunohistochemistry. Results Allergen challenge produced patchy, crater-like, and leucocyte-rich epithelial damage sites. At 1 , 5, and 24 h damage was associated with poorly differentiated epithel ial restitution cells. Already at 1 h the epithelial craters had a flo or of flattened restitution cells and the damaged areas comprised <1% of the mucosal surface area !whole-mount preparations). In contrast, c ryo sections displayed large areas (approximate to 20%, 1 h) of denuda tion. Epithelial, and subepithelial (fibroblasts, smooth muscle) proli feration was increased 5 and 24 h after challenge (P < 0.01). Conclusi on Within Ih allergen challenge has induced patchy damage sites where epithelial restitution is already advanced; although easily produced b y cryosectioning frank denudation was not evident in whole-mount prepa rations. The present findings may explain the well maintained, functio nal tightness of allergic airways displaying epithelial damage, sheddi ng, and even denudation. The present data also suggest the possibility that epithelial damage-restitution may be causative to allergic airwa y remodelling.