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Invariant natural killer T cells: Linking inflammation and neovascularization in human atherosclerosis.
MedLine Citation:
PMID:  20979229     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 α-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.
Authors:
Emmanouil Kyriakakis; Marco Cavallari; Jan Andert; Maria Philippova; Christoph Koella; Valery Bochkov; Paul Erne; S Brian Wilson; Lucia Mori; Barbara C Biedermann; Therese J Resink; Gennaro De Libero
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-9-2
Journal Detail:
Title:  European journal of immunology     Volume:  -     ISSN:  1521-4141     ISO Abbreviation:  -     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-10-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory for Signal Transduction, Department of Biomedicine, Basel University Hospital, Basel, Switzerland.
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