Phospholipase C gamma 2 is essential for specific functions of Fc epsilon R and Fc gamma R. J Immunol 2002 Dec 15;169(12):6743-52
Date
12/10/2002Pubmed ID
12471105DOI
10.4049/jimmunol.169.12.6743Scopus ID
2-s2.0-0037114147 (requires institutional sign-in at Scopus site) 68 CitationsAbstract
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.
Author List
Wen R, Jou ST, Chen Y, Hoffmeyer A, Wang DAuthors
Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinRenren Wen PhD Adjunct Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBiological Transport
Calcium
Cations, Divalent
Cell Degranulation
Cytokines
Enzyme Activation
Immunity, Innate
Immunoglobulin E
Isoenzymes
Macrophages, Peritoneal
Mast Cells
Mice
Mice, Knockout
Mitogen-Activated Protein Kinases
Passive Cutaneous Anaphylaxis
Phagocytosis
Phospholipase C gamma
Receptors, IgE
Receptors, IgG
Transcription, Genetic
Type C Phospholipases