A role for bronchial epithelial autotaxin in ventilator-induced lung injury

Nikitopoulou, Ioanna; Ninou, Ioanna; Manitsopoulos, Nikolaos; Dimopoulou, Ioanna; Orfanos, Stylianos E.; Aidinis, Vassilis; Kotanidou, Anastasia

BACKGROUND: The pathophysiology of acute respiratory distress syndrome (ARDS) may eventually result in heterogeneous lung collapse and edema-flooded airways, predisposing the lung to progressive tissue damage known as ventilator-induced lung injury (VILI). Autotaxin (ATX; ENPP2), the enzyme largely responsible for extracellular lysophosphatidic acid (LPA) production, has been suggested to play a pathogenic role in, among others, pulmonary inflammation and fibrosis. METHODS: C57BL/6 mice were subjected to low and high tidal volume mechanical ventilation using a small animal ventilator: respiratory mechanics were evaluated, and plasma and bronchoalveolar lavage fluid (BALF) samples were obtained. Total protein concentration was determined, and lung histopathology was further performed RESULTS: Injurious ventilation resulted in increased BALF levels of ATX. Genetic deletion of ATX from bronchial epithelial cells attenuated VILI-induced pulmonary edema. CONCLUSION: ATX participates in VILI pathogenesis.