Mononuclear-cell-derived microparticles attenuate endothelial inflammation by transfer of miR-142-3p in a CD39 dependent manner.

Abstract

Plasma microparticles (MP) bear functional active ectonucleotidases of the CD39 family with implications in vascular inflammation. MP appear to be able to fuse with cells and transfer genetic information. Here, we tested whether levels of different immunomodulatory microRNAs (miRs) in plasma MP are modulated by CD39 after experimental hepatectomy. We further investigated whether horizontal transfer of miR-142-3p between mononuclear (MNC) and endothelial cells via MP is regulated by purinergic signaling. Partial hepatectomy was performed in C57BL/6 wild type and Cd39 null mice. MP were collected via ultracentrifugation. MNC were stimulated with nucleotides and nucleosides, in vitro, and tested for miR-142-3p levels. Fusion of MNC-derived MP and endothelial cells with subsequent transfer of miR-142-3p was imaged by flow cytometry and confocal microscopy. Endothelial inflammation and apoptosis were quantified after transfection with miR-142-3p. Significantly lower miR-142-3p levels were observed in plasma MP of Cd39 null mice after partial hepatectomy, when compared to C57BL/6 wild types (p < 0.05). In contrast to extracellular nucleotides, anti-inflammatory adenosine significantly increased miR-142-3p levels in MNC-derived MP, in vitro (p < 0.05). MNC-derived MP are able to transfer miR-142-3p to endothelial cells by fusion. Transfection of endothelial cells with miR-142-3p decreased TNF-α levels (p < 0.05) and endothelial apoptosis (p < 0.05). MiR-142-3p levels in MNC-derived MP are modulated by nucleoside signaling and might reflect compensatory responses in vascular inflammation. Our data suggest the transfer of genetic information via shed MP as a putative mechanism of intercellular communication-with implications in organ regeneration.

• Authors: Stephanie Kuhn, Katrin Splith, Cindy Ballschuh, Linda Feldbrügge, Felix Krenzien, Georgi Atanasov, Christian Benzing, Hans-Michael Hau, Cornelius Engelmann, Thomas Berg, Jan Schulte Am Esch, Johann Pratschke, Simon C Robson, Moritz Schmelzle
• Journal: Purinergic signalling (Purinergic Signal) Vol. 14 Issue 4 Pg. 423-432 (12 2018) ISSN: 1573-9546 [Electronic] Netherlands
• PMID: 30244433 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• MIRN142 microRNA, rat
• MicroRNAs
• Apyrase
• CD39 antigen

Topics

• Animals
• Antigens, CD (genetics, metabolism)
• Apoptosis (genetics)
• Apyrase (genetics, metabolism)
• Cell Proliferation (genetics)
• Cell-Derived Microparticles (metabolism)
• Endothelial Cells (metabolism)
• Inflammation (genetics)
• Mice, Inbred C57BL
• MicroRNAs (genetics)