Epithelial injury, inflammation, and repair in the hamster lung following intratracheal instillation of enzyme-generated oxidants

Oxidant-induced inflammatory and morphologic changes evoked by intratracheally instilled glucose, active glucose oxidase, and lactoperoxidase in hamsters are described. Similar solutions containing heat-denatured (DE) glucose oxidase served as a control treatment. During the 7-week post-treatment period, animals were sacrificed and lavaged, and their lungs were preserved for later study. Although a neutrophil-rich alveolitis was observed initially in both groups, the leukocytic influx and mild morphologic changes in DE-treated animals resolved within 7 days. In contrast, glucose oxidase mixtures caused necrotic alveolar epithelium, fibrin-like exudate, and significantly higher neutrophil and protein levels in bronchoalveolar lavage fluid (BALF) after 1 day. At 4 days, type II cell hyperplasia was extensive and BALF levels of all inflammatory cell types were significantly greater than BALF counts in DE animals. By 7 days, BALF macrophage and lymphocyte levels remained significantly elevated, and epithelial hyperplasia coincided with marked increases in lung hydroxyproline and interstitial cells. BALF parameters suggested that inflammation induced by glucose oxidase resolved within 15 days, yet total hydroxyproline levels remained elevated at 15 days and epithelial lesions were still detectable at 29 days. Oxidant-induced inflammation and epithelial injury were transient and preceded moderate collagen deposition.