Abstract
Phagocytosis is a primary defense program orchestrated by monocytes/macrophages. Unregulated phagocytosis can lead to pathological conditions. In the current study we have demonstrated that Wnt5a stimulates phagocytosis through PI3 kinase-Rac1 and lipid-raft-dependent processes. Wnt5a-mediated augmentation in phagocytosis is suppressed by blocking expression of the putative Wnt5a receptor Frizzled 5. Enhanced phagocytosis of bacteria by Wnt5a-Fz5 signaling increases the secretion of proinflammatory cytokines, but not the bacterial killing rate. Furthermore, a small molecule inhibitor of Wnt production, IWP-2, which reduces secretion of functionally active Wnt5a, not only suppresses both phagocytosis and the secretion of proinflammatory cytokines but also accelerates the bacterial killing rate.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Cytokines / immunology
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Cytokines / metabolism
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Escherichia coli / immunology*
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Escherichia coli / physiology
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Escherichia coli Infections / immunology*
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Escherichia coli Infections / metabolism
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Escherichia coli Infections / microbiology
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Frizzled Receptors / genetics
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Frizzled Receptors / immunology
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Frizzled Receptors / metabolism
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Host-Pathogen Interactions / immunology
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Immunoblotting
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Inflammation Mediators / immunology
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Inflammation Mediators / metabolism
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L Cells
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Macrophages / immunology
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Macrophages / metabolism
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Macrophages / microbiology
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Membrane Microdomains / metabolism
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Mice
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Mice, Inbred C57BL
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Microscopy, Confocal
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Neuropeptides / metabolism
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Phagocytosis / immunology*
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Phosphatidylinositol 3-Kinases / metabolism
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RNA Interference
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Signal Transduction / immunology
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Wnt Proteins / genetics
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Wnt Proteins / immunology*
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Wnt Proteins / metabolism
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Wnt-5a Protein
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rac GTP-Binding Proteins / metabolism
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rac1 GTP-Binding Protein
Substances
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Cytokines
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Frizzled Receptors
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Fzd5 protein, mouse
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Inflammation Mediators
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Neuropeptides
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Rac1 protein, mouse
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Wnt Proteins
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Wnt-5a Protein
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Wnt5a protein, mouse
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rac GTP-Binding Proteins
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rac1 GTP-Binding Protein