Acute Lung Injury Regulation by Hyaluronan

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), have high mortality rates with few treatment options. An important regulatory factor in the pathology observed in ALI/ARDS is a disruption of the pulmonary endothelial barrier which, in combination with epithelial barrier disruption, causes leakage of fluid, protein and cells into lung airspaces. Degradation of the glycosaminoglycan, hyaluronan (HA), is involved in reduction of the endothelial glycocalyx, disruption of endothelial cell-cell contacts and activation of HA binding proteins upregulated in ALI/ARDS which promote 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 dichotomous 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.