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

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. Electronic supplementary material The online version of this article (10.1186/s12931-019-1099-6) contains supplementary material, which is available to authorized users.

Madecassoside Protects Against LPS-Induced Acute Lung Injury via Inhibiting TLR4/NF-κB Activation and Blood-Air Barrier Permeability

“…Acute lung injury (ALI) is a life-threatening clinical syndrome in human. The pathophysiological characteristic of ALI is uncontrolled and acute inflammatory disorder showing by destruction of both capillary endothelial cells and alveolar cells, infiltration of inflammatory mediators into the lung and then inducing the occurrence of ALI caused (Chen et al, 2019;Yang et al, 2019). Lipopolysaccharides (LPS), a main component of the outer membrane of gram-negative, has been applied to be an inducer of ALI (Kristof et al, 1998).…”

The number of circulating endothelial progenitor cells from septic patients are associated with different infectious organisms

“…Fan et al has veri ed that exogenous administration of EPCs is bene cial in cercal ligation and puncture (CLP) induced sepsis, and it can improve lung vascular integrity and reduce mortality in sepsis [28]. We have found that LPS induced lung injury repairment may be correlated with improvement of EPCs numbers and functions induced by high density lipoprotein mimetic peptide reverse-D-4F [29]. EPCs may be a therapeutic target for sepsis induced lung impairment in the future.…”

Vagal α7nAChR signaling regulates α7nAChR+Sca1+ cells during lung injury repair

“…4e). Coexpression of α7nAChR and VE-cadherin was found in the periphery of blood vessels or capillaries in the bone It has been reported that EPC transplantation could improve LPS-induced acute lung injury [27,[39][40][41]. In 23 patients with pneumonia, the proportion of EPCs in peripheral blood MNCs was increased.…”

“…It has been reported that EPC transplantation could improve LPS-induced acute lung injury [ 27 , 39 – 41 ]. In 23 patients with pneumonia, the proportion of EPCs in peripheral blood MNCs was increased.…”