Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1998-9-10
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
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
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
161
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2383-90
pubmed:dateRevised
2011-10-27
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
pubmed:year
1998
pubmed:articleTitle
Migration inhibitory factor induces killing of Leishmania major by macrophages: dependence on reactive nitrogen intermediates and endogenous TNF-alpha.
pubmed:affiliation
Institute of Clinical Microbiology and Immunology, University of Erlangen-Nürnberg, Germany.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't