Specialized Pro-resolving Mediators Regulate Alveolar Fluid Clearance during Acute Respiratory Distress Syndrome

OBJECTIVE: Acute respiratory distress syndrome (ARDS) is an acute and lethal clinical syndrome that is characterized by the injury of alveolar epithelium, which impairs active fluid transport in the lung, and impedes the reabsorption of edema fluid from the alveolar space. This review aimed to discuss the role of pro-resolving mediators on the regulation of alveolar fluid clearance (AFC) in ARDS. DATA SOURCES: Articles published up to September 2017 were selected from the PubMed, with the keywords of “alveolar fluid clearance” or “lung edema” or “acute lung injury” or “acute respiratory distress syndrome”, and “specialized pro-resolving mediators” or “lipoxin” or “resolvin” or “protectin” or “maresin” or “alveolar epithelial cells” or “aspirin-triggered lipid mediators” or “carbon monoxide and heme oxygenase” or “annexin A1”. STUDY SELECTION: We included all relevant articles published up to September 2017, with no limitation of study design. RESULTS: Specialized pro-resolving mediators (SPMs), as the proinflammatory mediators, not only upregulated epithelial sodium channel, Na,K-ATPase, cystic fibrosis transmembrane conductance regulator (CFTR), and aquaporins levels, but also improved Na,K-ATPase activity to promote AFC in ARDS. In addition to the direct effects on ion channels and pumps of the alveolar epithelium, the SPMs also inhibited the inflammatory cytokine expression and improved the alveolar epithelial cell repair to enhance the AFC in ARDS. CONCLUSIONS: The present review discusses a novel mechanism for pulmonary edema fluid reabsorption. SPMs might provide new opportunities to design “reabsorption-targeted” therapies with high degrees of precision in controlling ALI/ARDS.