Vis enkel innførsel

dc.contributor.authorNymo, Stig Haugset
dc.contributor.authorNiyonzima, Nathalie
dc.contributor.authorEspevik, Terje
dc.contributor.authorMollnes, Tom Eirik
dc.date.accessioned2017-02-09T13:01:24Z
dc.date.available2017-02-09T13:01:24Z
dc.date.issued2014-07-05
dc.description.abstractCholesterol crystals are known to be a hallmark of atherosclerosis with recent studies demonstrating deposition of these crystals in early fatty streak formation as well as penetrating the intima following plaque rupture. Inflammation has also become a central focus in atheroma development and endothelial cell activation is recognized as necessary for the recruitment of inflammatory cells to the plaque. However, the extent to which cholesterol crystals can induce inflammation and activate endothelial cells is not known. To investigate this, we developed a novel model activating human umbilical vein endothelial cells using lepirudin anticoagulated human whole blood. We found that cholesterol crystals caused a marked and dose-dependent increase in the adhesion molecules E-selectin and ICAM-1 on the surface of the endothelial cells after incubation with whole blood. There was no activation of the cells when the crystals were incubated in medium alone, or in human serum, despite substantial crystal-induced complement activation in serum. Complement inhibitors at the C3 and C5 levels reduced the whole blood induced endothelial cell activation by up to 89% (p < 0.05) and abolished TNF release (p < 0.01). Finally, the TNF inhibitor infliximab reduced endothelial activation to background levels (p < 0.05). In conclusion, these data demonstrate that endothelial activation by cholesterol crystals is mediated by complement-dependent TNF release, and suggests that complement-inhibition might have a role in alleviating atherosclerosis-induced inflammation.en_US
dc.descriptionSubmitted manuscript version. Published version at <a href=http://dx.doi.org/10.1016/j.imbio.2014.06.006>http://dx.doi.org/10.1016/j.imbio.2014.06.006</a>. License in accordance with the journal's policy – <a href=http://creativecommons.org/licenses/by-nc-nd/4.0/>CC-BY-NC-ND</a>.en_US
dc.identifier.citationImmunobiology 2014, 219(10):786-792en_US
dc.identifier.cristinIDFRIDAID 1174171
dc.identifier.doi10.1016/j.imbio.2014.06.006
dc.identifier.issn0171-2985
dc.identifier.urihttps://hdl.handle.net/10037/10284
dc.identifier.urnURN:NBN:no-uit_munin_9268
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.projectIDNorges forskningsråd: 223255en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectAtherosclerosisen_US
dc.subjectCholesterol crystalsen_US
dc.subjectComplementen_US
dc.subjectEndothelial cellsen_US
dc.subjectInnate immunityen_US
dc.subjectTNFen_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Generell immunologi: 478en_US
dc.titleCholesterol crystal-induced endothelial cell activation is complement-dependent and mediated by TNFen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US


Tilhørende fil(er)

Thumbnail

Denne innførselen finnes i følgende samling(er)

Vis enkel innførsel