Reverse-D-4F improves endothelial progenitor cell function and attenuates LPS-induced acute lung injury

Respiratory Research

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[1] 0000 0000 9588 091X, grid.440653.0, Department of Pharmaceutical Sciences, Binzhou Medical College, Yantai City, People’s Republic of China;0000 0004 1790 6079, grid.268079.2, Experimental Center for Medical Research, Weifang Medical University, Weifang City, People’s Republic of China;Department of Emergency Medicine, the second Affiliated Hospital of Shandong First Medical University, Tai-an City, People’s Republic of China;Institute of Preschool Education, Jinan Preschool Education College, Jinan City, People’s Republic of China;Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Shandong First Medical University, Tai-an City, People’s Republic of China;Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Shandong First Medical University, Tai-an City, People’s Republic of China;Heart Center of Shandong First Medical University, Tai-an City, People’s Republic of China;

关键词: Acute lung injury;    Endothelial progenitor cells;    Reverse D-4F;    Apolipoprotein A-I;    Endothelial nitric oxide synthase;   

DOI  :  10.1186/s12931-019-1099-6

来源: publisher

【 摘 要 】

BackgroundPatients with acute lung injury (ALI) have increased levels of pro-inflammatory mediators, which impair endothelial progenitor cell (EPC) function. Increasing the number of EPC and alleviating EPC dysfunction induced by pro-inflammatory mediators play important roles in suppressing ALI development. Because the high density lipoprotein reverse-D-4F (Rev-D4F) improves EPC function, we hypothesized that it might repair lipopolysaccharide (LPS)-induced lung damage by improving EPC numbers and function in an LPS-induced ALI mouse model.MethodsLPS was used to induce ALI in mice, and then the mice received intraperitoneal injections of Rev-D4F. Immunohistochemical staining, flow cytometry, MTT, transwell, and western blotting were used to assess the effect of Rev-D4F on repairment of lung impairment, and improvement of EPC numbers and function, as well as the signaling pathways involved.ResultsRev-D4F inhibits LPS-induced pulmonary edema and decreases plasma levels of the pro-inflammatory mediators TNF-α and ET-1 in ALI mice. Rev-D4F inhibited infiltration of red and white blood cells into the interstitial space, reduced lung injury-induced inflammation, and restored injured pulmonary capillary endothelial cells. In addition, Rev-D4F increased numbers of circulating EPC, stimulated EPC differentiation, and improved EPC function impaired by LPS. Rev-D4F also acted via a PI3-kinase-dependent mechanism to restore levels of phospho-AKT, eNOS, and phospho-eNOS suppressed by LPS.ConclusionsThese findings indicate that Rev-D4F has an important vasculoprotective role in ALI by improving the EPC numbers and functions, and Rev-D4F reverses LPS-induced EPC dysfuncion partially through PI3K/AKT/eNOS signaling pathway.

【 授权许可】

CC BY