Selective Suppression of Interleukin-12 Induction after Macrophage Receptor Ligation
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- Fayyaz S. Sutterwala
- From the *Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140; the ‡Department of Pediatrics, Cornell University Medical College, New York,10021; and the §Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, 10021
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- Gary J. Noel
- From the *Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140; the ‡Department of Pediatrics, Cornell University Medical College, New York,10021; and the §Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, 10021
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- Raphael Clynes
- From the *Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140; the ‡Department of Pediatrics, Cornell University Medical College, New York,10021; and the §Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, 10021
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- David M. Mosser
- From the *Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140; the ‡Department of Pediatrics, Cornell University Medical College, New York,10021; and the §Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, 10021
抄録
<jats:p>Interleukin (IL)-12 is a monocyte- and macrophage-derived cytokine that plays a crucial role in both the innate and the acquired immune response. In this study, we examined the effects that ligating specific macrophage receptors had on the induction of IL-12 by lipopolysaccharide (LPS). We report that ligation of the macrophage Fcγ, complement, or scavenger receptors inhibited the induction of IL-12 by LPS. Both mRNA synthesis and protein secretion were diminished to near-undetectable levels following receptor ligation. Suppression was specific to IL-12 since IL-10 and tumor necrosis factor-α (TNF-α) production were not inhibited by ligating macrophage receptors. The results of several different experimental approaches suggest that IL-12 downregulation was due to extracellular calcium influxes that resulted from receptor ligation. First, preventing extracellular calcium influxes, by performing the assays in EGTA, abrogated FcγR-mediated IL-12(p40) mRNA suppression. Second, exposure of macrophages to the calcium ionophores, ionomycin or A23187, mimicked receptor ligation and inhibited IL-12(p40) mRNA induction by LPS. Finally, bone marrow–derived macrophages from FcR γ chain–deficient mice, which fail to flux calcium after receptor ligation, failed to inhibit IL-12(p40) mRNA induction. These results indicate that the calcium influxes that occur as a result of receptor ligation are responsible for inhibiting the induction of IL-12 by LPS. Hence, the ligation of phagocytic receptors on macrophages can lead to a dramatic decrease in IL-12 induction. This downregulation may be a way of limiting proinflammatory responses of macrophages to extracellular pathogens, or suppressing the development of cell-mediated immunity to intracellular pathogens.</jats:p>
収録刊行物
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- The Journal of Experimental Medicine
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The Journal of Experimental Medicine 185 (11), 1977-1985, 1997-06-02
Rockefeller University Press
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詳細情報 詳細情報について
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- CRID
- 1363951795894392064
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- NII論文ID
- 30017415305
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- ISSN
- 15409538
- 00221007
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