NOX enzymes: potential target for the treatment of acute lung injury

Abstract

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), is characterized by acute inflammation, disruption of the alveolar-capillary barrier, and in the organizing stage by alveolar pneumocytes hyperplasia and extensive lung fibrosis. The cellular and molecular mechanisms leading to the development of ALI/ARDS are not completely understood, but there is evidence that reactive oxygen species (ROS) generated by inflammatory cells as well as epithelial and endothelial cells are responsible for inflammatory response, lung damage, and abnormal repair. Among all ROS-producing enzymes, the members of NADPH oxidases (NOXs), which are widely expressed in different lung cell types, have been shown to participate in cellular processes involved in the maintenance of lung integrity. It is not surprising that change in NOXs' expression and function is involved in the development of ALI/ARDS. In this context, the use of NOX inhibitors could be a possible therapeutic perspective in the management of this syndrome. In this article, we summarize the current knowledge concerning some cellular aspects of NOXs localization and function in the lungs, consider their contribution in the development of ALI/ARDS and discuss the place of NOX inhibitors as potential therapeutical target.

Fig. 1

Histological hallmarks of acute respiratory distress syndrome during the exudative and the proliferative phases. a, b Lung sections stained with hematoxylin and eosin (H&E) obtained from biopsy of ARDS subjects during the exudative phase. a Deposition of hyaline membranes (HM) on the epithelial side of the basement membrane. At this stage, the presence of detached epithelial type II cells from the alveolar wall (EII) is also apparent. b The presence of the interstitial edema (E). The necrosis of endothelial cells (En) and the formation of thrombus associated with the margination of neutrophil (TN) are also obvious at this stage. Original magnification ×400 (a and b), ×500 for enlarged insert. c, d Lung sections stained with (H&E) obtained from biopsy of ARDS subjects during the proliferative phase. c, d The evident hyperplasia of epithelial type II cells (EII) and an extended zone of interstitial (IN) fibro-proliferation. Note the presence of myofibroblasts in the parenchyma (MF). Original magnifications ×200 (c), ×400 (d)