| http://purl.uniprot.org/citations/18987138 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18987138 | http://www.w3.org/2000/01/rdf-schema#comment | "The protein tyrosine phosphatase SHP-1 is a crucial negative regulator of cytokine signaling and inflammatory gene expression, both in the immune system and in the central nervous system (CNS). Mice genetically lacking SHP-1 (me/me) display severe inflammatory demyelinating disease following inoculation with the Theiler's murine encephalomyelitis virus (TMEV) compared to infected wild-type mice. Therefore, it became essential to investigate the mechanisms of TMEV-induced inflammation in the CNS of SHP-1-deficient mice. Herein, we show that the expression of several genes relevant to inflammatory demyelination in the CNS of infected me/me mice is elevated compared to that in wild-type mice. Furthermore, SHP-1 deficiency led to an abundant and exclusive increase in the infiltration of high-level-CD45-expressing (CD45(hi)) CD11b(+) Ly-6C(hi) macrophages into the CNS of me/me mice, in concert with the development of paralysis. Histological analyses of spinal cords revealed the localization of these macrophages to extensive inflammatory demyelinating lesions in infected SHP-1-deficient mice. Sorted populations of CNS-infiltrating macrophages from infected me/me mice showed increased amounts of viral RNA and an enhanced inflammatory profile compared to wild-type macrophages. Importantly, the application of clodronate liposomes effectively depleted splenic and CNS-infiltrating macrophages and significantly delayed the onset of TMEV-induced paralysis. Furthermore, macrophage depletion resulted in lower viral loads and lower levels of inflammatory gene expression and demyelination in the spinal cords of me/me mice. Finally, me/me macrophages were more responsive than wild-type macrophages to chemoattractive stimuli secreted by me/me glial cells, indicating a mechanism for the increased numbers of infiltrating macrophages seen in the CNS of me/me mice. Taken together, these findings demonstrate that infiltrating macrophages in SHP-1-deficient mice play a crucial role in promoting viral replication by providing abundant viral targets and contribute to increased proinflammatory gene expression relevant to the effector mechanisms of macrophage-mediated demyelination."xsd:string |
| http://purl.uniprot.org/citations/18987138 | http://purl.org/dc/terms/identifier | "doi:10.1128/jvi.01210-08"xsd:string |
| http://purl.uniprot.org/citations/18987138 | http://purl.uniprot.org/core/author | "Hudson C.A."xsd:string |
| http://purl.uniprot.org/citations/18987138 | http://purl.uniprot.org/core/author | "Massa P.T."xsd:string |
| http://purl.uniprot.org/citations/18987138 | http://purl.uniprot.org/core/author | "Christophi G.P."xsd:string |
| http://purl.uniprot.org/citations/18987138 | http://purl.uniprot.org/core/author | "Gruber R.C."xsd:string |
| http://purl.uniprot.org/citations/18987138 | http://purl.uniprot.org/core/author | "Panos M."xsd:string |
| http://purl.uniprot.org/citations/18987138 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/18987138 | http://purl.uniprot.org/core/name | "J Virol"xsd:string |
| http://purl.uniprot.org/citations/18987138 | http://purl.uniprot.org/core/pages | "522-539"xsd:string |
| http://purl.uniprot.org/citations/18987138 | http://purl.uniprot.org/core/title | "Modulation of macrophage infiltration and inflammatory activity by the phosphatase SHP-1 in virus-induced demyelinating disease."xsd:string |
| http://purl.uniprot.org/citations/18987138 | http://purl.uniprot.org/core/volume | "83"xsd:string |
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