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

Acute respiratory distress syndrome is a life-threatening critical syndrome resulting largely from the accumulation of and the inability to clear pulmonary edema. Protectin DX, an endogenously produced lipid mediator, is believed to exert anti-inflammatory and pro-resolution effects. Protectin DX (5 µg/kg) was injected i.v. 8 h after LPS (14 mg/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 by upregulating sodium channel and Na, K-ATPase protein expression levels in vivo and in vitro. Protectin DX also increased the activity of Na, K-ATPase and upregulated P-Akt via inhibiting Nedd4–2 in vivo. In addition, protectin DX enhanced the subcellular distribution of sodium channels and Na, K-ATPase, which were specifically localized to the apical and basal membranes of primary rat ATII cells. Furthermore, BOC-2, Rp-cAMP, and LY294002 blocked the increased alveolar fluid clearance in 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. Treatment that involves boosting levels of a signaling molecule could help reduce fluid on the lungs in acute respiratory distress syndrome (ARDS). This condition usually affects critically ill patients with illnesses such as pneumonia or sepsis, and leads to severe inflammation and flooding of the lungs with fluid. This prevents microscopic air sacs called aveoli from processing oxygen and carbon dioxide effectively. At present there is no effective management for the condition. Now, Sheng-Wei Jin at Wenzhou Medical University, China, and co-workers have shown that boosting levels of a signaling molecule called protectin DX can help with aveolar fluid clearance in rats. They found that protectin DX activates sodium channels within the aveoli, helping clear fluid, and also acts as an anti-inflammatory and pro-resolving mediator to protect lung tissues from further injury.