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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2011

Open Access 01-12-2011 | Research

Increased circulating leukocyte numbers and altered macrophage phenotype correlate with the altered immune response to brain injury in metallothionein (MT) -I/II null mutant mice

Authors: Michael W Pankhurst, William Bennett, Matthew TK Kirkcaldie, Adrian K West, Roger S Chung

Published in: Journal of Neuroinflammation | Issue 1/2011

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Abstract

Background

Metallothionein-I and -II (MT-I/II) is produced by reactive astrocytes in the injured brain and has been shown to have neuroprotective effects. The neuroprotective effects of MT-I/II can be replicated in vitro which suggests that MT-I/II may act directly on injured neurons. However, MT-I/II is also known to modulate the immune system and inflammatory processes mediated by the immune system can exacerbate brain injury. The present study tests the hypothesis that MT-I/II may have an indirect neuroprotective action via modulation of the immune system.

Methods

Wild type and MT-I/II-/- mice were administered cryolesion brain injury and the progression of brain injury was compared by immunohistochemistry and quantitative reverse-transcriptase PCR. The levels of circulating leukocytes in the two strains were compared by flow cytometry and plasma cytokines were assayed by immunoassay.

Results

Comparison of MT-I/II-/- mice with wild type controls following cryolesion brain injury revealed that the MT-I/II-/- mice only showed increased rates of neuron death after 7 days post-injury (DPI). This coincided with increases in numbers of T cells in the injury site, increased IL-2 levels in plasma and increased circulating leukocyte numbers in MT-I/II-/- mice which were only significant at 7 DPI relative to wild type mice. Examination of mRNA for the marker of alternatively activated macrophages, Ym1, revealed a decreased expression level in circulating monocytes and brain of MT-I/II-/- mice that was independent of brain injury.

Conclusions

These results contribute to the evidence that MT-I/II-/- mice have altered immune system function and provide a new hypothesis that this alteration is partly responsible for the differences observed in MT-I/II-/- mice after brain injury relative to wild type mice.
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Metadata
Title
Increased circulating leukocyte numbers and altered macrophage phenotype correlate with the altered immune response to brain injury in metallothionein (MT) -I/II null mutant mice
Authors
Michael W Pankhurst
William Bennett
Matthew TK Kirkcaldie
Adrian K West
Roger S Chung
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2011
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-8-172

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