Abstract
The clearance of apoptotic cells is critical for both tissue homeostasis and the resolution of inflammation. We found that the TAM receptor tyrosine kinases Axl and Mer had distinct roles as phagocytic receptors in these two settings, in which they exhibited divergent expression, regulation and activity. Mer acted as a tolerogenic receptor in resting macrophages and during immunosuppression. In contrast, Axl was an inflammatory response receptor whose expression was induced by proinflammatory stimuli. Axl and Mer differed in their ligand specificities, ligand-receptor complex formation in tissues, and receptor shedding upon activation. These differences notwithstanding, phagocytosis by either protein was strictly dependent on receptor activation triggered by bridging of TAM receptor-ligand complexes to the 'eat-me' signal phosphatidylserine on the surface of apoptotic cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / immunology
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Axl Receptor Tyrosine Kinase
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Bone Marrow Cells / immunology
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Bone Marrow Cells / metabolism
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Cells, Cultured
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dendritic Cells / ultrastructure
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Gene Expression / drug effects
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Gene Expression / immunology
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Immunoblotting
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / immunology
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Intercellular Signaling Peptides and Proteins / metabolism
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Lipopolysaccharides / immunology
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Lipopolysaccharides / pharmacology
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Macrophages / immunology*
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Macrophages / metabolism
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Mice, Inbred C57BL
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Mice, Knockout
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Microscopy, Confocal
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Microscopy, Electron, Scanning
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Phagocytosis / immunology
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Protein Binding / immunology
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / immunology*
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Proto-Oncogene Proteins / metabolism
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / immunology*
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Receptor Protein-Tyrosine Kinases / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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c-Mer Tyrosine Kinase
Substances
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Intercellular Signaling Peptides and Proteins
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Lipopolysaccharides
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Proto-Oncogene Proteins
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growth arrest-specific protein 6
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Mertk protein, mouse
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Receptor Protein-Tyrosine Kinases
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c-Mer Tyrosine Kinase
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Axl Receptor Tyrosine Kinase
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AXL receptor tyrosine kinase, mouse