Protectin DX increases alveolar fluid clearance in rats with 2 lipopolysaccharide-induced acute lung injury

Acute respiratory distress syndrome is a life-threatening critical syndrome resulting largely from the accumulation of and inability to clear pulmonary edema. Protectin DX, as an endogenously produced lipid mediator, is believed to exert anti-inflammatory and pro-resolution actions. Protectin DX (5ug/kg) was injected i.v. 8 h after LPS (14mg/kg) administration and alveolar fluid clearance was measured in live rats (n=8). In primary rat ATII epithelial cells, Protectin DX (3.605×10-3 mg/L) was added to the culture medium with LPS for 6 h. Protectin DX improved alveolar fluid clearance (9.65±1.60 vs. 15.85±1.49, p<0.0001) and decreased pulmonary edema and lung injury in LPS-induced lung injury in rats. Protectin DX markedly regulated alveolar fluid clearance with up-regulating the protein expression of sodium channel and Na,K-ATPase in vivo and in vitro. Protectin DX also increased the activity of Na,K-ATPase and up-regulated P-Akt via inhibition of Nedd4-2 in vivo. Besides, Protectin DX enhanced the subcellular distribution of sodium channel and Na,K-ATPase, specifically localized to the apical and basal membrane of the primary rat ATII cells. Furthermore, BOC-2, Rp-cAMP, and LY294002 blocked the increased alveolar fluid clearance response to Protectin DX. Protectin DX stimulates alveolar fluid clearance through a mechanism partly dependent on alveolar epithelial sodium channel and Na,K-ATPase activation via the ALX/PI3K/Nedd4-2 signaling pathway.