Microvesicles with mitochondrial content are increased in patients with sepsis and associated with inflammatory...

Endothelial activation plays an important role in sepsis-mediated inflammation, but the triggering factors have not been fully elucidated. Microvesicles carrying mitochondrial content (mitoMVs) have been implicated in several diseases and shown to induce endothelial activation.

To explore whether mitoMVs constitute a subset of MVs isolated from plasma of patients with sepsis and contribute to endothelial activation.

MVs were isolated from human plasma and characterized by confocal microscopy and flow cytometry. Proinflammatory cytokines, including interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α, and soluble vascular cell adhesion molecule (sVCAM)-1 were detected by ELISA. Human umbilical vein endothelial cells (HUVECs) were stimulated with the circulating MVs to evaluate their effect on endothelial activation.

MitoMVs were observed in plasma from patients with sepsis. Compared with those in healthy controls, expression of MVs, mitoMVs, proinflammatory cytokines and sVCAM-1 was increased. The number of mitoMVs was positively associated with TNF-α and sVCAM-1. In vitro, compared with MVs isolated from the plasma of healthy controls, MVs isolated from the plasma of patients with sepsis induced expression of OAS2, RSAD2, and CXCL10 in HUVECs. MitoMVs were taken up by HUVECs, and sonication of MVs significantly reduced the uptake of mitoMVs by HUVECs and expression of the above three type I IFN-dependent genes.

MitoMVs are increased in the plasma of patients with sepsis, which induces elevated expression of type I IFN-dependent genes. This suggests that circulating mitoMVs activate the type I IFN signalling pathway in endothelial cells and lead to endothelial activation.