Abstract
Whole spleen cell cultures from SCID mice release high levels of IFN-gamma when exposed to heat-killed Listeria monocytogenes (HKL). This microbe-induced and T cell-independent response depends on both macrophages (MPhi) and NK cells: HKL-stimulated MPhi release TNF-alpha and IL-12, which together activate NK cells for IFN-gamma release. We show here that this cytokine-mediated activation cascade can be modulated by a mAb against the MPhi surface glycoprotein F4/80. HKL-induced IL-12, TNF-alpha, and IFN-gamma in SCID whole spleen cell cultures was inhibited by coincubation with anti-F4/80 mAb whereas IL-1 and IL-10 were enhanced. Both effects were apparent at mRNA and protein release levels. Whereas inhibitory activities were F4/80 Ag specific, stimulatory effects were Fc dependent and nonspecific. Furthermore, cytokine inhibition by anti-F4/80 was only apparent when MPhi and NK cells were present simultaneously and in close vicinity, indicating that direct cell-to-cell contact is a prerequisite. These data suggest a novel pathway for microbe-induced MPhi/NK cell interaction involving direct cell-to-cell signaling and give the first evidence for a functional role of the MPhi surface glycoprotein F4/80.
MeSH terms
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Adjuvants, Immunologic / metabolism
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Adjuvants, Immunologic / pharmacology*
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Animals
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Antibodies, Monoclonal / metabolism
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Antibodies, Monoclonal / pharmacology*
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Antibody Specificity
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Antigens, Differentiation / immunology*
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Cell Communication / immunology
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Cells, Cultured
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Coculture Techniques
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Contact Inhibition / immunology
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Cytokines / biosynthesis
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Cytokines / genetics
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Cytokines / metabolism
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Epitopes / physiology
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Female
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Hot Temperature
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Immunity, Innate / immunology
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Immunoglobulin Fab Fragments / physiology
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Immunosuppressive Agents / metabolism
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Immunosuppressive Agents / pharmacology
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Interferon-gamma / antagonists & inhibitors
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Interferon-gamma / metabolism
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Killer Cells, Natural / microbiology
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Kinetics
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Listeria monocytogenes / immunology*
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Macrophages / immunology*
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Macrophages / microbiology
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Male
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Mice
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Mice, SCID
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RNA, Messenger / biosynthesis
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
Substances
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Adjuvants, Immunologic
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Antibodies, Monoclonal
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Antigens, Differentiation
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Cytokines
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Epitopes
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Immunoglobulin Fab Fragments
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Immunosuppressive Agents
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RNA, Messenger
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monocyte-macrophage differentiation antigen
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Interferon-gamma