Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.1203604 on May 20, 2005

Published online before print May 20, 2005
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(Journal of Leukocyte Biology. 2005;78:393-400.)
© 2005 by Society for Leukocyte Biology

Detection of the inhibitory neurotransmitter GABA in macrophages by magnetic resonance spectroscopy

D. J. Stuckey*, D. C. Anthony{dagger}, J. P. Lowe*, J. Miller{ddagger}, W. M. Palm*, P. Styles*, V. H. Perry§, A. M. Blamire* and N. R. Sibson*,1

* Experimental Neuroimaging Group, Department of Biochemistry,
{dagger} Experimental Neuropathology Laboratory, Department of Pharmacology, and
{ddagger} Sir William Dunn School of Pathology, University of Oxford, United Kingdom; and
§ CNS Inflammation Group, School of Biological Sciences, University of Southampton, United Kingdom

1 Correspondence: University Laboratory of Physiology, University of Oxford, OX1 3PT, UK. E-mail: Nicola.Sibson{at}physiol.ox.ac.uk

Macrophages are key components of the inflammatory response to tissue injury, but their activities can exacerbate neuropathology. High-resolution magnetic resonance spectroscopy was used to identify metabolite levels in perchloric acid extracts of cultured cells of the RAW 264.7 murine macrophage line under resting and lipopolysaccharide-activated conditions. Over 25 metabolites were identified including {gamma}-aminobutyric acid (GABA), an inhibitory neurotransmitter not previously reported to be present in macrophages. The presence of GABA was also demonstrated in extracts of human peripheral blood monocyte-derived macrophages. This finding suggests that there may be communication between damaged central nervous system (CNS) tissue and recruited macrophages and resident microglia, which could help orchestrate the immune response. On activation, lactate, glutamine, glutamate, and taurine levels were elevated significantly, and GABA and alanine were reduced significantly. Strong resonances from glutathione, evident in the macrophage two-dimensional 1H spectrum, suggest that this may have potential as a noninvasive marker of macrophages recruited to the CNS, as it is only present at low levels in normal brain. Alternatively, a specific combination of spectroscopic changes, such as lactate, alanine, glutathione, and polyamines, may prove to be the most accurate means of detecting macrophage recruitment to the CNS.

Key Words: inflammation • MRS • mouse • brain






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