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Reverse-D-4F improves endothelial progenitor cell function and attenuates LPS-induced acute lung injury
- Source :
- Respiratory Research, Vol 20, Iss 1, Pp 1-11 (2019)
- Publication Year :
- 2019
- Publisher :
- BMC, 2019.
-
Abstract
- Abstract Background Patients 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. Methods LPS 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. Results Rev-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. Conclusions These 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.
Details
- Language :
- English
- ISSN :
- 1465993X
- Volume :
- 20
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Respiratory Research
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.be64054ac7b44377bc29b56ddb0a71c3
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s12931-019-1099-6