Abstract
Phospholipase Cgamma2 (PLCgamma2) plays a critical role in the functions of the B cell receptor in B cells and of the FcRgamma chain-containing collagen receptor in platelets. Here we report that PLCgamma2 is also expressed in mast cells and monocytes/macrophages and is activated by cross-linking of Fc(epsilon)R and Fc(gamma)R. Although PLCgamma2-deficient mice have normal development and numbers of mast cells and monocytes/macrophages, we demonstrate that PLCgamma2 is essential for specific functions of Fc(epsilon)R and Fc(gamma)R. While PLCgamma2-deficient mast cells have normal mitogen-activated protein kinase activation and cytokine production at mRNA levels, the mutant cells have impaired Fc(epsilon)R-mediated Ca(2+) flux and inositol 1,4,5-trisphosphate production, degranulation, and cytokine secretion. As a physiological consequence of the effect of PLCgamma2 deficiency, the mutant mice are resistant to IgE-mediated cutaneous inflammatory skin reaction. Macrophages from PLCgamma2-deficient mice have no detectable Fc(gamma)R-mediated Ca(2+) flux; however, the mutant cells have normal Fc(gamma)R-mediated phagocytosis. Moreover, PLCgamma2 plays a nonredundant role in Fc(gamma)R-mediated inflammatory skin reaction.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biological Transport / genetics
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Biological Transport / immunology
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Calcium / metabolism
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Cations, Divalent / metabolism
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Cell Degranulation / genetics
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Cell Degranulation / immunology
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Cytokines / genetics
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Cytokines / metabolism
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Enzyme Activation / genetics
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Enzyme Activation / immunology
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Immunity, Innate / genetics
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Immunoglobulin E / physiology
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Isoenzymes / deficiency
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Isoenzymes / genetics
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Isoenzymes / physiology*
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Macrophages, Peritoneal / enzymology
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Macrophages, Peritoneal / immunology
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Macrophages, Peritoneal / metabolism
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Mast Cells / enzymology
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Mast Cells / immunology
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Mast Cells / metabolism
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Mice
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Mice, Knockout
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Mitogen-Activated Protein Kinases / metabolism
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Passive Cutaneous Anaphylaxis
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Phagocytosis / genetics
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Phagocytosis / immunology
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Phospholipase C gamma
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Receptors, IgE / immunology
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Receptors, IgE / metabolism
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Receptors, IgE / physiology*
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Receptors, IgG / immunology
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Receptors, IgG / metabolism
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Receptors, IgG / physiology*
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Transcription, Genetic / immunology
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Type C Phospholipases / deficiency
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Type C Phospholipases / genetics
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Type C Phospholipases / physiology*
Substances
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Cations, Divalent
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Cytokines
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Isoenzymes
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Receptors, IgE
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Receptors, IgG
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Immunoglobulin E
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Mitogen-Activated Protein Kinases
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Type C Phospholipases
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Phospholipase C gamma
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Calcium