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 epithelial damage, and of the ensuing epithelial restitution processes in allergic airways. Objective To examine epithelial damage and restitution in allergen challenged guinea-pig trachea. Methods Whole-mount techniques, transmission and scanning electron microscopy, cryosectioning, and histochemical staining were used. Cell proliferation was monitored 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 epithelial restitution cells. Already at 1 h the epithelial craters had a floor of flattened restitution cells and the damaged areas comprised <1% of the mucosal surface area !whole-mount preparations). In contrast, cryo sections displayed large areas (approximate to 20%, 1 h) of denudation. Epithelial, and subepithelial (fibroblasts, smooth muscle) proliferation was increased 5 and 24 h after challenge (P < 0.01). Conclusion Within Ih allergen challenge has induced patchy damage sites where epithelial restitution is already advanced; although easily produced by cryosectioning frank denudation was not evident in whole-mount preparations. The present findings may explain the well maintained, functional tightness of allergic airways displaying epithelial damage, shedding, and even denudation. The present data also suggest the possibility that epithelial damage-restitution may be causative to allergic airway remodelling.