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01.12.2009 | Research

Proinflammatory and prothrombotic effects on human vascular endothelial cells of Immune-cell-derived LIGHT

verfasst von: S Celik, V Shankar, A Richter, H-J Hippe, M Akhavanpoor, F Bea, C Erbel, S Urban, N Blank, N Wambsganss, HA Katus, TJ Dengler

Erschienen in: European Journal of Medical Research | Ausgabe 4/2009

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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 LTßR 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 and Results

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 ~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-γ 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.

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Titel: Proinflammatory and prothrombotic effects on human vascular endothelial cells of Immune-cell-derived LIGHT
verfasst von: S Celik
V Shankar
A Richter
H-J Hippe
M Akhavanpoor
F Bea
C Erbel
S Urban
N Blank
N Wambsganss
HA Katus
TJ Dengler
Publikationsdatum: 01.12.2009
Verlag: BioMed Central
Erschienen in: European Journal of Medical Research / Ausgabe 4/2009
Elektronische ISSN: 2047-783X
DOI: https://doi.org/10.1186/2047-783X-14-4-147

Springer Medizin

Abstract

Objective

Methods and Results

Conclusion

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