Pulmonary reexpansion causes xanthine oxidase-induced apoptosis in rat lung

Abstract

Saito, Satoshi, Jun-ichi Ogawa, and Yoshihiro Minamiya. Pulmonary reexpansion causes xanthine oxidase-induced apoptosis in rat lung. Am J Physiol Lung Cell Mol Physiol 289: L400 -L406, 2005. First published May 6, 2005; doi:10.1152/ajplung.00136.2005.-The pathogenesis of reexpansion pulmonary edema is not yet fully understood. We therefore studied its mechanism in a rat model in which the left lung was collapsed by bronchial occlusion for 1 h and then reexpanded and ventilated for an additional 3 h. We then evaluated the production of reactive oxygen species in the lungs using fluorescent imaging and cerium deposition electron microscopic techniques and the incidence of apoptosis using the TdT-mediated dUTP-digoxigenin nick end labeling (TUNEL) method. We found that pulmonary reexpansion induced production of reactive oxygen species and then apoptosis, mainly in endothelial and alveolar type II epithelial cells. Endothelial cells and alveolar type I and II epithelial cells in the reexpanded lung were positive for TUNEL and cleaved caspase-3. DNA fragmentation was also observed in the reexpanded lung. In addition, wet-dry ratios obtained with reexpanded lungs were significantly higher than those obtained with control lungs, indicating increased fluid content. All of these effects were attenuated by pretreating rats with a specific xanthine oxidase inhibitor, sodium (Ϫ)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one. It thus appears that pulmonary reexpansion activates xanthine oxidase in both endothelial and alveolar type II epithelial cells and that the reactive oxygen species produced by the enzyme induce apoptosis among the endothelial and alveolar type I and II epithelial cells that make up the pulmonary water-air barrier, leading to reexpansion pulmonary edema.reactive oxygen species; caspase-3; type II alveolar epithelial cell; reoxygenation REEXPANSION PULMONARY EDEMA (RPE) is a rare complication of the treatment of lung collapse secondary to pneumothorax, pleural effusion, or atelectasis. Although physicians generally believe that, unlike acute respiratory distress syndrome (ARDS), RPE does not require intensive care, the outcome of RPE is reportedly fatal in 20% of patients (17). Moreover, reexpansion after atelectatic storage for hypothermic preservation of lungs before transplantation may be responsible for postpreservation and postreperfusion lung injury (7).The mechanism responsible for RPE is not fully understood. It has been suggested that after atelectasis the mechanical stresses related to lung inflation may cause RPE (28). This effect has also been mentioned as a contributor to the pathogenesis of postpreservation lung injury (9). In addition, some evidence suggests changes in alveolar surfactant may contribute to RPE (26,31), and a number of investigators have reported that neutrophil accumulation in the lung induced by various chemokines (e.g., IL-8 and monocyte chemoattractant protein-1), chemical mediators, and adhesion molecules (24, 30) plays a major role in ...

Role of nitric oxide synthases in elastase-induced emphysema

“…Indeed, alveolar type 2 cells express NADPH oxidase and xanthine oxidase and are an important source of superoxide in the lung. 29,30 Alternatively, the accumulation of nitrated proteins in alveolar type 2 cells may reflect a constitutive or elastase-induced vulnerability of these cells to nitrosative stress.…”

Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury

“…Ventilation with hypoxic gas, rather than stopping ventilation altogether, during ischemia was used to avoid atelectasis while still maintaining ischemia. Atelectasis and reexpansion has been shown to induce injury involving edema, oxidant generation, and apoptosis (13,42,46). This reexpansioninduced injury could obscure the effects of I/R injury, an issue we wished to avoid.…”

The Effects of Oxidative Stress on the Liver and Ileum in Rats Caused by One-Lung Ventilation

“…Experimental and clinical studies have shown that collapse and re-expansion arising during one-lung ventilation causes free radicals to emerge, and that this leads to re-expansion injury [17][18][19]. Hypoxic vasoconstriction arises as a result of bronchial occlusion, and reperfusion occurs together with re-expansion [3,4].…”