Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0208138 on June 12, 2008

Published online before print June 12, 2008
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(Journal of Leukocyte Biology. 2008;84:736-740.)
© 2008 by Society for Leukocyte Biology

Chondroitin sulfate disaccharide stimulates microglia to adopt a novel regulatory phenotype

Stefanie Ebert*,1, Tobias Schoeberl*,1, Yana Walczak*, Katharina Stoecker*, Thomas Stempfl{dagger}, Christoph Moehle{dagger}, Bernhard H. F. Weber* and Thomas Langmann*,2

* Institute of Human Genetics, University of Regensburg, Regensburg, Germany; and
{dagger} Center of Excellence for Fluorescent Bioanalytics, Regensburg, Germany

2 Correspondence: Institute of Human Genetics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. E-mail: thomas.langmann{at}klinik.uni-regensburg.de

A disaccharide degradation product of chondrotin sulfate proteoglycan-disaccharide (CSPG-DS) has been implicated previously in the inhibition of neurodegeneration by influencing microglia activation. In this study, genome-wide microarray analysis was used to identify specific gene expression profiles of CSPG-DS-stimulated BV-2 microglia-like cells. Gene products involved in phagocytosis, detoxification, migration, immune regulation, and antigen presentation were found to be altered significantly. These findings were replicated and compared with IFN-{gamma}-stimulated primary microglia using real-time quantitative RT-PCR validation. Importantly, a unique transcriptional phenotype with anti-inflammatory and IFN-{gamma} counter-regulatory properties partially related to alternatively activated macrophages was identified. Using functional cell assays, we found that CSPG-DS-stimulated microglia possess increased phagocytic capacity but lack direct cytotoxic effects such as secretion of NO. Furthermore, conditioned media from CSPG-DS-treated microglia did not diminish the viability or cause apoptosis of cultured photoreceptor cells and partially rescued these cells from IFN-{gamma}-induced apoptosis. Taken together, our data provide a unique transcript dataset and important in vitro findings about the functional properties of CSPG-DS-activated microglia. These might be starting points to explore the in vivo role of CSPG-DS as a bioactive microglia regulator and its potential, therapeutic application in immune-related, neurodegenerative disorders.

Key Words: neurodegeneration • microglia activation • neuroprotection • proteoglycans




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