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- W1979339075 endingPage "387" @default.
- W1979339075 startingPage "371" @default.
- W1979339075 abstract "SHP-1 is a protein tyrosine phosphatase that negatively regulates cytokine signaling and inflammatory gene expression. Mice genetically lacking SHP-1 (me/me) display severe inflammatory demyelinating disease following intracranial inoculation with the BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) compared to infected wild-type mice. Furthermore, SHP-1-deficient mice show a profound and predominant infiltration of blood-derived macrophages into the CNS following intracerebral injection of TMEV, and these macrophages are concentrated in areas of demyelination in brain and spinal cord. In the present study we investigated the role of SHP-1 in controlling CNS inflammatory demyelination following a peripheral instead of an intracerebral inoculation of TMEV. Surprisingly, we found that while wild-type mice were entirely refractory to intraperitoneal (IP) infection by TMEV, in agreement with previous studies, all SHP-1-deficient mice displayed profound macrophage neuroinvasion and macrophage-mediated inflammatory demyelination. Moreover, SHP-1 deficiency led to increased expression of inflammatory molecules in macrophages, serum, and CNS following IP infection with TMEV. Importantly, pharmacological depletion of peripheral macrophages significantly decreased both paralysis and CNS viral loads in SHP-1-deficient mice. In addition, peripheral MCP-1 neutralization attenuated disease severity, decreased macrophage infiltration into the CNS, and decreased monocyte numbers in the blood of SHP-1-deficient mice, implicating MCP-1 as an important mediator of monocyte migration between multiple tissues. These results demonstrate that peripheral TMEV infection results in a unique evolution of macrophage-mediated demyelination in SHP-1-deficient mice, implicating SHP-1 in the control of neuroinvasion of inflammatory macrophages and neurotropic viruses into the CNS." @default.
- W1979339075 created "2016-06-24" @default.
- W1979339075 creator A5042396093 @default.
- W1979339075 creator A5084448524 @default.
- W1979339075 date "2009-12-01" @default.
- W1979339075 modified "2023-10-16" @default.
- W1979339075 title "Central Neuroinvasion and Demyelination by Inflammatory Macrophages After Peripheral Virus Infection is Controlled by SHP-1" @default.
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- W1979339075 doi "https://doi.org/10.1089/vim.2009.0052" @default.
- W1979339075 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2883524" @default.