The complement inhibitor low molecular weight dextran sulfate prevents TLR4-induced phenotypic and functional maturation of human dendritic cells.

Details

Serval ID
serval:BIB_193520B5234E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The complement inhibitor low molecular weight dextran sulfate prevents TLR4-induced phenotypic and functional maturation of human dendritic cells.
Journal
Journal of Immunology
Author(s)
Spirig R., van Kooten C., Obregon C., Nicod L., Daha M., Rieben R.
ISSN
1550-6606[electronic]
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
181
Number
2
Pages
878-890
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
Low molecular weight dextran sulfate (DXS) has been reported to inhibit the classical, alternative pathway as well as the mannan-binding lectin pathway of the complement system. Furthermore, it acts as an endothelial cell protectant inhibiting complement-mediated endothelial cell damage. Endothelial cells are covered with a layer of heparan sulfate (HS), which is rapidly released under conditions of inflammation and tissue injury. Soluble HS induces maturation of dendritic cells (DC) via TLR4. In this study, we show the inhibitory effect of DXS on human DC maturation. DXS significantly prevents phenotypic maturation of monocyte-derived DC and peripheral myeloid DC by inhibiting the up-regulation of CD40, CD80, CD83, CD86, ICAM-1, and HLA-DR and down-regulates DC-SIGN in response to HS or exogenous TLR ligands. DXS also inhibits the functional maturation of DC as demonstrated by reduced T cell proliferation, and strongly impairs secretion of the proinflammatory mediators IL-1beta, IL-6, IL-12p70, and TNF-alpha. Exposure to DXS leads to a reduced production of the complement component C1q and a decreased phagocytic activity, whereas C3 secretion is increased. Moreover, DXS was found to inhibit phosphorylation of IkappaB-alpha and activation of NF-kappaB. These findings suggest that DXS prevents TLR-induced maturation of human DC and may therefore be a useful reagent to impede the link between innate and adaptive immunity.
Keywords
Cell Adhesion Molecules/metabolism, Cell Differentiation, Cell Proliferation, Complement System Proteins/immunology, Complement System Proteins/metabolism, Cytokines/metabolism, Dendritic Cells/drug effects, Dendritic Cells/immunology, Dextran Sulfate/metabolism, Dextran Sulfate/pharmacology, Humans, I-kappa B Kinase/metabolism, Inflammation Mediators/metabolism, Interleukin-10/metabolism, Lectins, C-Type/metabolism, Macrophage-1 Antigen/metabolism, Monocytes/cytology, Monocytes/immunology, NF-kappa B/metabolism, Phagocytosis, Receptors, Cell Surface/metabolism, T-Lymphocytes/drug effects, T-Lymphocytes/immunology, Toll-Like Receptor 4/immunology, Toll-Like Receptor 4/metabolism
Pubmed
Web of science
Create date
12/02/2010 15:41
Last modification date
20/08/2019 12:49
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