Hyaluronan Regulation of Acute Lung Injury

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), have high mortality rates with few treatment options. A crucial factor in the pathology observed in ALI/ARDS is a disruption of the pulmonary endothelial barrier which causes leakage of fluid, protein and cells into lung airspaces. Degradation of the glycosaminoglycan hyaluronan (HA) by hyaluronidase enzymes and reactive oxygen species (ROS) is involved in reduction of the endothelial glycocalyx, disruption of endothelial cell-cell contacts and activation of HA binding proteins in ALI/ARDS resulting in a loss of pulmonary vascular integrity. In contrast, exogenous administration of high molecular weight HA has been shown to be protective in several models of ALI. This review focuses on the role of HA to both promote and inhibit ALI based on its size and the HA binding proteins present. Further, potential therapeutic applications of high molecular weight HA in treating ALI/ARDS are discussed.