A Novel Pathway of Cellular Activation Mediated by Antiphospholipid Antibody-Induced Extracellular Vesicles.

CONCLUSIONS: Anti-β2GPI antibodies caused formation of an endothelial cell inflammasome and release of EV that were enriched in mature IL-1β, had a distinct miRNA profile, and caused endothelial activation. However, activation was not inhibited by an IL-1β antibody, IL-1 receptor antagonist or IL-1 receptor siRNA. Endothelial cell activation by EV required IRAK4 phosphorylation and was inhibited by pretreatment of cells with TLR7 siRNA or RNase A, which degrades single-stranded RNA. Profiling of miRNA in EV released from endothelial cells incubated with β2GPI and either control IgG or anti-β2GPI antibodies revealed numerous differences in the content of specific miRNAs, including a significant decrease in mIR126. These observations demonstrate that although anti-β2GPI-derived endothelial EV contain IL-1β, they activate unstimulated endothelial cells through a TLR7 and single-stranded RNA dependent pathway. Alterations in miRNA content may contribute to the ability of EV derived from endothelial cells exposed to anti-β2GPI antibodies to activate unstimulated endothelial cells in a paracrine manner. This article is protected by copyright. All rights reserved. PMID: 26264622 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Tags: J Thromb Haemost Source Type: research