Effects of hydrogen peroxide on the guinea-pig tracheobronchial mucosa in vivo

Lumenal entry of plasma (mucosal exudation) is a key feature of airway inflammation. In airways challenged with histamine-type mediators and allergen the mucosal exudation response occurs without causing epithelial derangement and without increased airway absorption. In contrast, reactive oxygen metabolites may cause mucosal damage. In this study, involving guinea-pig airways, we have examined effects of H₂O₂ on airway exudation and absorption in vivo. Vehicle or H₂O₂ (0.1 and 0.5 M ) was superfused onto the tracheobronchial mucosal surface through an oro-tracheal catheter. ¹²⁵I-albumin, given intravenously, was determined in tracheobronchial tissue and in lavage fluids 10 min after challenge as an index of mucosal exudation of plasma. The tracheobronchial mucosa was also examined by scanning electron microscopy. In separate animals, ^99mTc-DTPA was superfused 20 min after vehicle or H₂O₂ (0.1 and 0.5 M ) had been given. A gamma camera determined the disappearance rate of ^99mTc-DTPA from the airways as an index of airway absorption. The high dose of H₂O₂ (0.5 M ) produced epithelial damage, increased the absorption of ^99mTc-DTPA (P < 0.001), and increased the exudation of plasma (P < 0.001). Notably, it appeared that all extravasated plasma had entered the airway lumen within 10 min. These data demonstrate that H₂O₂ differs from exudative autacoids such as histamine by causing both epithelial damage and plasma exudation responses. These data also agree with the view that the epithelial lining determines the rate of absorption and is responsible for the valve-like function that allows lumenal entry of extravasated bulk plasma without any increased inward perviousness.