Source:http://linkedlifedata.com/resource/pubmed/id/15661915
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2005-1-21
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pubmed:abstractText |
IFN-alpha/beta-mediated functions promote production of MIP-1alpha (or CCL3) by mediating the recruitment of MIP-1alpha-producing macrophages to the liver during early infection with murine CMV. These responses are essential for induction of NK cell inflammation and IFN-gamma delivery to support effective control of local infection. Nevertheless, it remains to be established if additional chemokine functions are regulated by IFN-alpha/beta and/or play intermediary roles in supporting macrophage trafficking. The chemokine MCP-1 (or CCL2) plays a distinctive role in the recruitment of macrophages by predominantly stimulating the CCR2 chemokine receptor. Here, we examine the roles of MCP-1 and CCR2 during murine CMV infection in liver. MCP-1 production preceded that of MIP-1alpha during infection and was dependent on IFN-alpha/beta effects for induction. Resident F4/80(+) liver leukocytes were identified as primary IFN-alpha/beta responders and major producers of MCP-1. Moreover, MCP-1 deficiency was associated with a dramatic reduction in the accumulation of macrophages and NK cells, as well as decreased production of MIP-1alpha and IFN-gamma in liver. These responses were also markedly impaired in mice with a targeted disruption of CCR2. Furthermore, MCP-1- and CCR2-deficient mice exhibited increased viral titers and elevated expression of the liver enzyme alanine aminotransferase in serum. These mice also had widespread virus-induced liver pathology and succumbed to infection. Collectively, these results establish MCP-1 and CCR2 interactions as factors promoting early liver inflammatory responses and define a mechanism for innate cytokines in regulation of chemokine functions critical for effective localized antiviral defenses.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCR2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ccl2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ccr2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL3,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL4,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Inflammatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Chemokine,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
174
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1549-56
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15661915-Animals,
pubmed-meshheading:15661915-Cell Movement,
pubmed-meshheading:15661915-Chemokine CCL2,
pubmed-meshheading:15661915-Chemokine CCL3,
pubmed-meshheading:15661915-Chemokine CCL4,
pubmed-meshheading:15661915-Cytokines,
pubmed-meshheading:15661915-Cytomegalovirus Infections,
pubmed-meshheading:15661915-Female,
pubmed-meshheading:15661915-Humans,
pubmed-meshheading:15661915-Immunity, Innate,
pubmed-meshheading:15661915-Inflammation,
pubmed-meshheading:15661915-Interferon Type I,
pubmed-meshheading:15661915-Kinetics,
pubmed-meshheading:15661915-Liver,
pubmed-meshheading:15661915-Macrophage Inflammatory Proteins,
pubmed-meshheading:15661915-Male,
pubmed-meshheading:15661915-Mice,
pubmed-meshheading:15661915-Mice, Inbred C57BL,
pubmed-meshheading:15661915-Mice, Knockout,
pubmed-meshheading:15661915-Muromegalovirus,
pubmed-meshheading:15661915-Receptors, CCR2,
pubmed-meshheading:15661915-Receptors, Chemokine,
pubmed-meshheading:15661915-Recombinant Proteins,
pubmed-meshheading:15661915-Viral Load
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pubmed:year |
2005
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pubmed:articleTitle |
Monocyte chemoattractant protein-1 and CCR2 interactions are required for IFN-alpha/beta-induced inflammatory responses and antiviral defense in liver.
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pubmed:affiliation |
Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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