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Background:Acute lung injury (ALI) is a severe disease with high mortality and poor prognosis.Protectin DX (PDX),a pro-resolving lipid mediator,exhibits protective effects in ALI.Our experiment aimed to explore the effects and related mechanisms of PDX in mice with ALI induced by lipopolysaccharide (LPS).Methods:BALB/c mice were randomly divided into five groups:sham,LPS,LPS plus 1 ng ofPDX (LPS + PDX-1 ng),LPS plus 10 ng ofPDX (LPS + PDX-10 ng),and LPS plus 100 ng ofPDX (LPS + PDX-100 ng).Bronchoalveolar lavage fluids (BALFs) were collected after 24 h,and total cells,polymorphonuclear leukocytes,monocyte-macrophages,and lymphocytes in BALF were enumerated.The concentration of interleukin (IL)-1 β3,IL-6,IL-10,tumor necrosis factor-alpha (TNF-α),macrophage inflammatory protein (MIP)-1 cα,and MIP-2 in BALF was determined,and histopathological changes of the lung were observed.The concentration of protein in BALF and lung wet/dry weight ratios were detected to evaluate pulmonary edema.After determining the optimal dose of PDX,neutrophil-platelet interactions in whole blood were evaluated by flow cytometry.Results:The highest dose of PDX (100 ng/mouse) failed to provide pulmonary protective effects,whereas lower doses of PDX (1 ng/mouse and 10 ng/mouse),especially 1 ng PDX,alleviated pulmonary histopathological changes,mitigated LPS-induced ALI and pulmonary edema,inhibited neutrophil infiltration,and reduced pro-inflammatory mediator (IL-1β,IL-6,TNF-α,and MIP-lα) levels.Meanwhile,1 ng PDX exhibited pro-resolving functions in ALI including upregulation of monocyte-macrophage numbers and anti-inflammatory mediator IL-l 0 levels.The flow cytometry results showed that PDX could inhibit neutrophil-platelet interactions in ALI.Conclusion:PDX exerts protective effects in LPS-inducedALI by mitigating pulmonary inflammation and abrogating neutrophil-platelet interactions.