Thromb Haemost 2012; 108(04): 730-741
DOI: 10.1160/TH12-03-0186
Wound Healing and Inflammation/Infection
Schattauer GmbH

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

Silvia Fischer*
1   Department of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany
,
Tobias Grantzow*
2   Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany
,
Judith I. Pagel
2   Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany
,
Marlene Tschernatsch
3   Department of Neurology, Justus-Liebig-University Giessen, Giessen
,
Markus Sperandio
2   Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany
,
Klaus T. Preissner
1   Department of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany
,
Elisabeth Deindl
2   Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany
› Author Affiliations
Financial support: These studies were generously supported by grants from the Deutsche Forschungsgemeinschaft (DFG, Bonn, Germany), including SFB 547, SPP 1190, FI 543/2-1, the Excellence cluster ”Cardio-pulmonary System“ (ECCPS) and the IRTG-1566 (PROMISE), received by Klaus T. Preissner and Silvia Fischer and by DFG grants SFB914 and SP621/4-1 to Markus Sperandio.
Further Information

Publication History

Received: 23 March 2012

Accepted after major revision: 16 July 2012

Publication Date:
29 November 2017 (online)

Summary

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 p2-inte-grin 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 kB 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.

* These authors contributed equally.


 
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