Cargando…

Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4

Low molecular weight fragmentation products of the polysaccharide of Hyaluronic acid (sHA) produced during inflammation have been shown to be potent activators of immunocompetent cells such as dendritic cells (DCs) and macrophages. Here we report that sHA induces maturation of DCs via the Toll-like...

Descripción completa

Detalles Bibliográficos
Autores principales: Termeer, Christian, Benedix, Frauke, Sleeman, Jonathon, Fieber, Christina, Voith, Ursula, Ahrens, Thomas, Miyake, Kensuke, Freudenberg, Marina, Galanos, Christopher, Simon, Jan Christoph
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196009/
https://www.ncbi.nlm.nih.gov/pubmed/11781369
http://dx.doi.org/10.1084/jem.20001858
_version_ 1782147975285309440
author Termeer, Christian
Benedix, Frauke
Sleeman, Jonathon
Fieber, Christina
Voith, Ursula
Ahrens, Thomas
Miyake, Kensuke
Freudenberg, Marina
Galanos, Christopher
Simon, Jan Christoph
author_facet Termeer, Christian
Benedix, Frauke
Sleeman, Jonathon
Fieber, Christina
Voith, Ursula
Ahrens, Thomas
Miyake, Kensuke
Freudenberg, Marina
Galanos, Christopher
Simon, Jan Christoph
author_sort Termeer, Christian
collection PubMed
description Low molecular weight fragmentation products of the polysaccharide of Hyaluronic acid (sHA) produced during inflammation have been shown to be potent activators of immunocompetent cells such as dendritic cells (DCs) and macrophages. Here we report that sHA induces maturation of DCs via the Toll-like receptor (TLR)-4, a receptor complex associated with innate immunity and host defense against bacterial infection. Bone marrow–derived DCs from C3H/HeJ and C57BL/10ScCr mice carrying mutant TLR-4 alleles were nonresponsive to sHA-induced phenotypic and functional maturation. Conversely, DCs from TLR-2–deficient mice were still susceptible to sHA. In accordance, addition of an anti–TLR-4 mAb to human monocyte–derived DCs blocked sHA-induced tumor necrosis factor α production. Western blot analysis revealed that sHA treatment resulted in distinct phosphorylation of p38/p42/44 MAP-kinases and nuclear translocation of nuclear factor (NF)-κB, all components of the TLR-4 signaling pathway. Blockade of this pathway by specific inhibitors completely abrogated the sHA-induced DC maturation. Finally, intravenous injection of sHA-induced DC emigration from the skin and their phenotypic and functional maturation in the spleen, again depending on the expression of TLR-4. In conclusion, this is the first report that polysaccharide degradation products of the extracellular matrix produced during inflammation might serve as an endogenous ligand for the TLR-4 complex on DCs.
format Text
id pubmed-2196009
institution National Center for Biotechnology Information
language English
publishDate 2002
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21960092008-04-14 Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4 Termeer, Christian Benedix, Frauke Sleeman, Jonathon Fieber, Christina Voith, Ursula Ahrens, Thomas Miyake, Kensuke Freudenberg, Marina Galanos, Christopher Simon, Jan Christoph J Exp Med Original Article Low molecular weight fragmentation products of the polysaccharide of Hyaluronic acid (sHA) produced during inflammation have been shown to be potent activators of immunocompetent cells such as dendritic cells (DCs) and macrophages. Here we report that sHA induces maturation of DCs via the Toll-like receptor (TLR)-4, a receptor complex associated with innate immunity and host defense against bacterial infection. Bone marrow–derived DCs from C3H/HeJ and C57BL/10ScCr mice carrying mutant TLR-4 alleles were nonresponsive to sHA-induced phenotypic and functional maturation. Conversely, DCs from TLR-2–deficient mice were still susceptible to sHA. In accordance, addition of an anti–TLR-4 mAb to human monocyte–derived DCs blocked sHA-induced tumor necrosis factor α production. Western blot analysis revealed that sHA treatment resulted in distinct phosphorylation of p38/p42/44 MAP-kinases and nuclear translocation of nuclear factor (NF)-κB, all components of the TLR-4 signaling pathway. Blockade of this pathway by specific inhibitors completely abrogated the sHA-induced DC maturation. Finally, intravenous injection of sHA-induced DC emigration from the skin and their phenotypic and functional maturation in the spleen, again depending on the expression of TLR-4. In conclusion, this is the first report that polysaccharide degradation products of the extracellular matrix produced during inflammation might serve as an endogenous ligand for the TLR-4 complex on DCs. The Rockefeller University Press 2002-01-07 /pmc/articles/PMC2196009/ /pubmed/11781369 http://dx.doi.org/10.1084/jem.20001858 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Termeer, Christian
Benedix, Frauke
Sleeman, Jonathon
Fieber, Christina
Voith, Ursula
Ahrens, Thomas
Miyake, Kensuke
Freudenberg, Marina
Galanos, Christopher
Simon, Jan Christoph
Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4
title Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4
title_full Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4
title_fullStr Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4
title_full_unstemmed Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4
title_short Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4
title_sort oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196009/
https://www.ncbi.nlm.nih.gov/pubmed/11781369
http://dx.doi.org/10.1084/jem.20001858
work_keys_str_mv AT termeerchristian oligosaccharidesofhyaluronanactivatedendriticcellsviatolllikereceptor4
AT benedixfrauke oligosaccharidesofhyaluronanactivatedendriticcellsviatolllikereceptor4
AT sleemanjonathon oligosaccharidesofhyaluronanactivatedendriticcellsviatolllikereceptor4
AT fieberchristina oligosaccharidesofhyaluronanactivatedendriticcellsviatolllikereceptor4
AT voithursula oligosaccharidesofhyaluronanactivatedendriticcellsviatolllikereceptor4
AT ahrensthomas oligosaccharidesofhyaluronanactivatedendriticcellsviatolllikereceptor4
AT miyakekensuke oligosaccharidesofhyaluronanactivatedendriticcellsviatolllikereceptor4
AT freudenbergmarina oligosaccharidesofhyaluronanactivatedendriticcellsviatolllikereceptor4
AT galanoschristopher oligosaccharidesofhyaluronanactivatedendriticcellsviatolllikereceptor4
AT simonjanchristoph oligosaccharidesofhyaluronanactivatedendriticcellsviatolllikereceptor4