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

Detection of the inhibitory neurotransmitter GABA in macrophages by magnetic resonance spectroscopy
Detection of the inhibitory neurotransmitter GABA in macrophages by magnetic resonance spectroscopy
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.
inflammation, MRS, mouse, brain
0741-5400
393-400
Stuckey, D.J.
acb7280d-6d37-454f-976b-f335352514cd
Anthony, D.C.
70fb8e27-4e74-4c72-b1b5-3a4ca0d6b8cf
Lowe, J.P.
ec367b00-76c3-4399-9ede-53b04930f3d1
Miller, J.
c03e1e6b-e158-418e-89ac-1d36a7549073
Palm, W.M.
bd904b71-c3b7-478a-a183-957b6caef22e
Styles, P.
9df179d2-0db7-4ae1-998f-db2a265fabe6
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Blamire, A.M.
44424cc8-eb88-45dd-910c-f5befb07945e
Sibson, N.R.
f693789d-e7ce-4323-b26a-86cef623120b
Stuckey, D.J.
acb7280d-6d37-454f-976b-f335352514cd
Anthony, D.C.
70fb8e27-4e74-4c72-b1b5-3a4ca0d6b8cf
Lowe, J.P.
ec367b00-76c3-4399-9ede-53b04930f3d1
Miller, J.
c03e1e6b-e158-418e-89ac-1d36a7549073
Palm, W.M.
bd904b71-c3b7-478a-a183-957b6caef22e
Styles, P.
9df179d2-0db7-4ae1-998f-db2a265fabe6
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Blamire, A.M.
44424cc8-eb88-45dd-910c-f5befb07945e
Sibson, N.R.
f693789d-e7ce-4323-b26a-86cef623120b

Stuckey, D.J., Anthony, D.C., Lowe, J.P., Miller, J., Palm, W.M., Styles, P., Perry, V.H., Blamire, A.M. and Sibson, N.R. (2005) Detection of the inhibitory neurotransmitter GABA in macrophages by magnetic resonance spectroscopy. Journal of Leukocyte Biology, 78 (2), 393-400. (doi:10.1189/jlb.1203604).

Record type: Article

Abstract

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.

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More information

Published date: 1 August 2005
Keywords: inflammation, MRS, mouse, brain

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Local EPrints ID: 56193
URI: http://eprints.soton.ac.uk/id/eprint/56193
ISSN: 0741-5400
PURE UUID: 04806d1b-4189-4b2b-91c1-b1424c210320

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Date deposited: 08 Aug 2008
Last modified: 15 Mar 2024 11:00

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Contributors

Author: D.J. Stuckey
Author: D.C. Anthony
Author: J.P. Lowe
Author: J. Miller
Author: W.M. Palm
Author: P. Styles
Author: V.H. Perry
Author: A.M. Blamire
Author: N.R. Sibson

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