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Invariant natural killer T cells : linking inflammation and neovascularization in human atherosclerosis

Kyriakakis, Emmanouil and Cavallari, Marco and Andert, Jan and Philippova, Maria and Koella, Christoph and Bochkov, Valery and Erne, Paul and Wilson, S. Brian and Mori, Lucia and Biedermann, Barbara C. and Resink, Therese J. and De Libero, Gennaro. (2010) Invariant natural killer T cells : linking inflammation and neovascularization in human atherosclerosis. European Journal of Immunology, Vol. 40, H. 11. pp. 3268-3279.

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Official URL: http://edoc.unibas.ch/dok/A6005744

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Abstract

Atherosclerosis, a chronic inflammatory lipid storage disease of large arteries, is complicated by cardiovascular events usually precipitated by plaque rupture or erosion. Inflammation participates in lesion progression and plaque rupture. Identification of leukocyte populations involved in plaque destabilization is important for effective prevention of cardiovascular events. This study investigates CD1d-expressing cells and invariant NKT cells (iNKT) in human arterial tissue, their correlation with disease severity and symptoms, and potential mechanisms for their involvement in plaque formation and/or destabilization. CD1d-expressing cells were present in advanced plaques in patients who suffered from cardiovascular events in the past and were most abundant in plaques with ectopic neovascularization. Confocal microscopy detected iNKT cells in plaques, and plaque-derived iNKT cell lines promptly produced proinflammatory cytokines when stimulated by CD1d-expressing APC-presenting -galactosylceramide lipid antigen. Furthermore, iNKT cells were diminished in the circulating blood of patients with symptomatic atherosclerosis. Activated iNKT cell-derived culture supernatants showed angiogenic activity in a human microvascular endothelial cell line HMEC-1-spheroid model of in vitro angiogenesis and strongly activated human microvascular endothelial cell line HMEC-1 migration. This functional activity was ascribed to IL-8 released by iNKT cells upon lipid recognition. These findings introduce iNKT cells as novel cellular candidates promoting plaque neovascularization and destabilization in human atherosclerosis.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Further Research Groups at DBM > Signal Transduction (Resink/Erne)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Nephrologie > Exp. Transplantationsimmunologie und Nephrologie (Palmer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Nephrologie > Exp. Transplantationsimmunologie und Nephrologie (Palmer)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Experimental Immunology (De Libero)
UniBasel Contributors:Resink, Thérèse J. and De Libero, Gennaro and Erne, Paul and Biedermann, Barbara C.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Academic Press
ISSN:0014-2980
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2012 16:23
Deposited On:08 Nov 2012 16:19

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