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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1998-9-10
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pubmed:abstractText |
Macrophage migration inhibitory factor (MIF) is a product of activated T cells, anterior pituitary cells, and macrophages. MIF plays an important role in LPS-induced shock and delayed-type hypersensitivity. Furthermore, MIF exhibits a proinflammatory spectrum of action, promoting TNF-alpha production by macrophages, and counter-regulates glucocorticoid suppression of cytokine production. Here, we report that purified recombinant MIF activates murine macrophages to kill Leishmania major, with maximal effects at concentrations above 1 microg/ml. This MIF-mediated activation is specific, since it can be blocked completely by anti-MIF mAb. The MIF-mediated activation is dependent on TNF-alpha produced endogenously by macrophages, because the administration of anti-TNF-alpha antiserum markedly reduced the MIF effect. No MIF-mediated activation was observed in macrophages derived from TNF receptor p55 knockout mice, thus demonstrating the requirement of the smaller TNF receptor molecule for autocrine TNF-alpha signaling. A highly specific inhibitor of the inducible nitric oxide synthase (iNOS), L-N6-(1-iminoethyl)lysine, dihydrochloride, also inhibited the action of MIF, suggesting an important role for iNOS in the antiparasitic properties of MIF. In line with this, no MIF-mediated activation was detected analyzing macrophages derived from iNOS-deficient mice. The effect of MIF was blocked completely by the macrophage-deactivating cytokines IL-10, IL-13, and TGF-beta. Finally, the expression of MIF mRNA and protein was up-regulated in lymph nodes of mice during the first week after infection with L. major. MIF therefore represents a cytokine involved not only in the recruitment of proinflammatory cells during infection but also in the complex regulation of the antimicrobial activity of these cells.
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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/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-13,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Migration-Inhibitory...,
http://linkedlifedata.com/resource/pubmed/chemical/NOS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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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 |
161
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2383-90
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pubmed:dateRevised |
2011-10-27
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pubmed:meshHeading |
pubmed-meshheading:9725234-Animals,
pubmed-meshheading:9725234-Bone Marrow Cells,
pubmed-meshheading:9725234-Cytotoxicity, Immunologic,
pubmed-meshheading:9725234-Female,
pubmed-meshheading:9725234-Humans,
pubmed-meshheading:9725234-Interleukin-10,
pubmed-meshheading:9725234-Interleukin-13,
pubmed-meshheading:9725234-Leishmania major,
pubmed-meshheading:9725234-Macrophage Activation,
pubmed-meshheading:9725234-Macrophage Migration-Inhibitory Factors,
pubmed-meshheading:9725234-Macrophages, Peritoneal,
pubmed-meshheading:9725234-Mice,
pubmed-meshheading:9725234-Mice, Inbred BALB C,
pubmed-meshheading:9725234-Mice, Inbred C3H,
pubmed-meshheading:9725234-Mice, Inbred C57BL,
pubmed-meshheading:9725234-Mice, Knockout,
pubmed-meshheading:9725234-Nitric Oxide,
pubmed-meshheading:9725234-Nitric Oxide Synthase,
pubmed-meshheading:9725234-Nitric Oxide Synthase Type II,
pubmed-meshheading:9725234-Recombinant Proteins,
pubmed-meshheading:9725234-Transforming Growth Factor beta,
pubmed-meshheading:9725234-Tumor Necrosis Factor-alpha
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pubmed:year |
1998
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pubmed:articleTitle |
Migration inhibitory factor induces killing of Leishmania major by macrophages: dependence on reactive nitrogen intermediates and endogenous TNF-alpha.
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pubmed:affiliation |
Institute of Clinical Microbiology and Immunology, University of Erlangen-Nürnberg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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