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• W4313347862 abstract "Abstract 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-α 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 μg/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-α produced endogenously by macrophages, because the administration of anti-TNF-α 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-α 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-β. 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." @default.
• W4313347862 created "2023-01-06" @default.
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• W4313347862 date "1998-09-01" @default.
• W4313347862 modified "2023-10-17" @default.
• W4313347862 title "Migration Inhibitory Factor Induces Killing of<i>Leishmania major</i>by Macrophages: Dependence on Reactive Nitrogen Intermediates and Endogenous TNF-α" @default.
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• W4313347862 doi "https://doi.org/10.4049/jimmunol.161.5.2383" @default.
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