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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/10704

Title: The inhibitory neurotransmitter glycine modulates macrophage activity by activation of neutral amino acid transporters
Authors: CARMANS, Sofie
HENDRIKS, Jerome
THEWISSEN, Kristof
VAN DEN EYNDEN, Jimmy
STINISSEN, Piet
RIGO, Jean-Michel
HELLINGS, Niels
Issue Date: 2010
Publisher: Wiley
Citation: JOURNAL OF NEUROSCIENCE RESEARCH, 88(11). p. 2420-2430
Abstract: Glycine, an important inhibitory neurotransmitter in the mammalian central nervous system (CNS), has been shown to modulate peripheral immune cell responses. In that respect, glycine levels are increased in several neuroinflammatory disorders, like amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). In this study, we show that glycine modulates macrophage effector functions implicated in CNS inflammation and in other related inflammatory conditions. We demonstrate that glycine does not affect the production of reactive oxygen species, but stimulates myelin phagocytosis and the production of the pro-inflammatory mediators nitric oxide (NO) and tumor necrosis factor (TNF)-F by rat macrophages. These effects of glycine are not mediated by the glycine receptor (GlyR) or by glycine transporters (GlyTs), since neither the GlyR antagonist strychnine, nor the antagonist of GlyT1 (ALX5407) reverse the observed effects. In contrast, 2-aminoisobutyric acid, a substrate of neutral amino acid transporters (NAATs), inhibits the glycine-mediated enhancement of myelin phagocytosis as well as of NO and TNF-F production. In conclusion, our findings demonstrate that glycine modulates macrophage function through activation of NAATs. Glycine may thereby influence immunological processes in inflammatory diseases involving macrophage activation and demyelination, including MS, and related conditions associated with altered glycine levels.
Notes: [Hellings, Niels] Hasselt Univ, Biomed Res Inst, B-3590 Diepenbeek, Belgium. Transnat Univ Limburg, Sch Life Sci, Diepenbeek, Belgium. RP Hellings, N, Hasselt Univ, Biomed Res Inst, Agoralaan Bldg C, B-3590 Diepenbeek, Belgium. EM niels.hellings@uhasselt.be
URI: http://hdl.handle.net/1942/10704
DOI: 10.1002/jnr.22395
ISI #: 000280436600011
ISSN: 0360-4012
Category: A1
Type: Journal Contribution
Validation: ecoom, 2011
Appears in Collections: Research publications

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