Proinflammatory and prothrombotic effects on human vascular endothelial cells of immune-cell-derived LIGHT.
Eur J Med Res
; 14(4): 147-56, 2009 Apr 16.
Article
em En
| MEDLINE
| ID: mdl-19380287
ABSTRACT
OBJECTIVE:
LIGHT (TNFSF 14) belongs to the tumor necrosis factor superfamily and is expressed by activated T cells as well as various types of antigen presenting cells. LIGHT binds to its cellular receptors TR2 and LTbetaR and has a co-stimulatory role in T cell activation. Here, we compared the relative expression of LIGHT in different immune cells and the biological activity of immune cell-derived LIGHT on endothelial cells. METHODS ANDRESULTS:
Surface expression of LIGHT and mRNA production by PBMC and isolated T cells (CD4+ or CD8+) significantly increased after stimulation with PMA (Phorbolester-12- Myristat-13-Acetat)+ionomycin. No LIGHT expression on PMA stimulated monocytes or monocytic-like THP-1 cells could be detected; differentiation of monocytes and THP-1 cells into macrophages, however, resulted in up-regulation of LIGHT. Supernatants of stimulated T cells contained higher concentrations of soluble LIGHT than macrophage supernatants normalized to cell numbers; release of soluble LIGHT was found to be dependent on metalloproteinase activity. Size determination of released soluble LIGHT by size exclusion chromatography revealed a molecular mass of approximately 60 kDa, suggesting a trimeric form. Released soluble LIGHT induced expression of proinflammatory antigens ICAM-1, tissue factor and IL-8 in human endothelial cells and caused apoptosis of IFN-g pretreated endothelial cells. Soluble LIGHT was detected at low levels in sera of healthy controls and was significantly enhanced in sera of patients with chronic hepatitis C and rheumatoid arthritis (24.93+/-9.41 vs. 129.53+/-49.14 and 172.13+/-77.64; p<0.0005).CONCLUSION:
These findings suggest that among immune cells activated T lymphocytes are the main source of soluble LIGHT with released amounts of soluble LIGHT markedly higher compared to platelets. Immune cell-derived membrane-bound and soluble trimeric LIGHT is biologically active, inducing proinflammatory changes in endothelial cells. Enhanced plasma levels of soluble LIGHT in patients with chronic infections suggest a role of LIGHT in systemic inflammatory activation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
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Leucócitos Mononucleares
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Linfócitos T
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Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral
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Macrófagos
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Eur J Med Res
Assunto da revista:
MEDICINA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Alemanha