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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
Citation
Pankhurst, MW and Bennett, W and Kirkcaldie, MTK and West, AK and Chung, RS, 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, Journal of Neuroinflammation, 8, (December) Article 172. ISSN 1742-2094 (2011) [Refereed Article]
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Copyright Statement
Licensed under Creative Commons Attribution 2.0 Generic (CC BY 2.0) http://creativecommons.org/licenses/by/2.0/
DOI: doi:10.1186/1742-2094-8-172
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.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | Metallothionein, cryolesion, brain injury, alternatively activated macrophages |
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Neurosciences |
| Research Field: | Central nervous system |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Pankhurst, MW (Mr Michael Pankhurst) |
| UTAS Author: | Bennett, W (Dr Bill Bennett) |
| UTAS Author: | Kirkcaldie, MTK (Dr Matthew Kirkcaldie) |
| UTAS Author: | West, AK (Professor Adrian West) |
| UTAS Author: | Chung, RS (Associate Professor Roger Chung) |
| ID Code: | 75273 |
| Year Published: | 2011 |
| Web of Science® Times Cited: | 15 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2012-01-19 |
| Last Modified: | 2017-11-06 |
| Downloads: | 508 View Download Statistics |
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