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Extracellular RNA promotes leukocyte recruitment in the vascular system by mobilising proinflammatory cytokines.
MedLine Citation:
PMID:  22836360     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
S Fischer; T Grantzow; J I Pagel; M Tschernatsch; M Sperandio; K T Preissner; E Deindl
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-26
Journal Detail:
Title:  Thrombosis and haemostasis     Volume:  108     ISSN:  0340-6245     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7608063     Medline TA:  Thromb Haemost     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Silvia Fischer, PhD, Department of Biochemistry, Medical School Justus-Liebig-University, Friedrichstr. 24, D-35392 Giessen, Germany, Tel: +49 641 9947440, Fax: +49 641 9947509, E-mail: silvia.fischer@biochemie.med.uni-giessen.de or Elisabeth Deindl, PhD, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University, Marchioninistr. 27, D-81377 Munich, Germany, Tel.: +49 89 2180 76504, Fax:+49 89 2180 76503, E-mail: Elisabeth.Deindl@med.uni-muenchen.de.
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