Extracellular RNA promotes leukocyte recruitment in the vascular system by mobilising proinflammatory cytokines

Thromb Haemost. 2012 Oct;108(4):730-41. doi: 10.1160/TH12-03-0186. Epub 2012 Jul 26.


Extracellular RNA (eRNA), released from cells under conditions of injury or vascular disease, acts as potent prothrombotic factor and promotes vascular hyperpermeability related to oedema formation in vivo. In this study, we aimed to investigate the mechanism by which eRNA triggers inflammatory processes, particularly associated with different steps of leukocyte recruitment. Using intravital microscopy of murine cremaster muscle venules, eRNA (but not DNA) significantly induced leukocyte adhesion and transmigration in vivo, which was comparable in its effects to the function of tumour-necrosis-factor-α (TNF-α). In vitro, eRNA promoted adhesion and transmigration of monocytic cells on and across endothelial cell monolayers. eRNA-induced monocyte adhesion in vitro was mediated by activation of the vascular endothelial growth factor (VEGF)/VEGF-receptor-2 system and was abolished by neutralising antibodies against intercellular adhesion molecule-1 or the β2-integrin Mac-1. Additionally, eRNA induced the release of TNF-α from monocytic cells in a time- and concentration-dependent manner, which involved activation of TNF-α-converting enzyme (TACE) as well as the nuclear factor κB signalling machinery. In vivo, inhibiton of TACE significantly reduced eRNA-induced leukocyte adhesion. Our findings present evidence that eRNA in connection with tissue/vascular damage provokes a potent inflammatory response by inducing leukocyte recruitment and by mobilising proinflammatory cytokines from monocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / physiology
  • ADAM17 Protein
  • Animals
  • Cell Adhesion / physiology
  • Cell Movement / physiology
  • Cells, Cultured
  • Cytokines / physiology*
  • Endothelium, Vascular / physiology
  • Extracellular Fluid / metabolism
  • Humans
  • Inflammation Mediators / physiology*
  • Intercellular Adhesion Molecule-1 / physiology
  • Leukocyte Rolling / physiology
  • Leukocytes / physiology*
  • Mice
  • Monocytes / physiology
  • Muscle, Skeletal / blood supply
  • NF-kappa B / physiology
  • RNA / genetics
  • RNA / metabolism*
  • Tumor Necrosis Factor-alpha / physiology
  • Vascular Endothelial Growth Factor A / physiology


  • Cytokines
  • Inflammation Mediators
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Intercellular Adhesion Molecule-1
  • RNA
  • ADAM Proteins
  • ADAM17 Protein
  • ADAM17 protein, human
  • Adam17 protein, mouse