Phospholipase Cγ2 is essential for specific functions of FcεR and FcγR

R Wen, ST Jou, Y Chen, A Hoffmeyer… - The Journal of …, 2002 - journals.aai.org
R Wen, ST Jou, Y Chen, A Hoffmeyer, D Wang
The Journal of Immunology, 2002journals.aai.org
Phospholipase Cγ2 (PLCγ2) plays a critical role in the functions of the B cell receptor in B
cells and of the FcRγ chain-containing collagen receptor in platelets. Here we report that
PLCγ2 is also expressed in mast cells and monocytes/macrophages and is activated by
cross-linking of FcεR and FcγR. Although PLCγ2-deficient mice have normal development
and numbers of mast cells and monocytes/macrophages, we demonstrate that PLCγ2 is
essential for specific functions of FcεR and FcγR. While PLCγ2-deficient mast cells have …
Abstract
Phospholipase Cγ2 (PLCγ2) plays a critical role in the functions of the B cell receptor in B cells and of the FcRγ chain-containing collagen receptor in platelets. Here we report that PLCγ2 is also expressed in mast cells and monocytes/macrophages and is activated by cross-linking of FcεR and FcγR. Although PLCγ2-deficient mice have normal development and numbers of mast cells and monocytes/macrophages, we demonstrate that PLCγ2 is essential for specific functions of FcεR and FcγR. While PLCγ2-deficient mast cells have normal mitogen-activated protein kinase activation and cytokine production at mRNA levels, the mutant cells have impaired FcεR-mediated Ca 2+ flux and inositol 1, 4, 5-trisphosphate production, degranulation, and cytokine secretion. As a physiological consequence of the effect of PLCγ2 deficiency, the mutant mice are resistant to IgE-mediated cutaneous inflammatory skin reaction. Macrophages from PLCγ2-deficient mice have no detectable FcγR-mediated Ca 2+ flux; however, the mutant cells have normal FcγR-mediated phagocytosis. Moreover, PLCγ2 plays a nonredundant role in FcγR-mediated inflammatory skin reaction.
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