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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


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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Licensed under Creative Commons Attribution 2.0 Generic (CC BY 2.0)

DOI: doi:10.1186/1742-2094-8-172


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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