Phospholipase C gamma 2 is essential for specific functions of Fc epsilon R and Fc gamma R.
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.
Wen
Renren
R
The Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, WI 53226, USA.
Jou
Shiann-Tarng
ST
Chen
Yuhong
Y
Hoffmeyer
Angelica
A
Wang
Demin
D
D000818:Animals; D001692:Biological Transport / Q000235:genetics / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D015550:Cell Degranulation / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D007073:Immunoglobulin E / Q000502:physiology; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010323:Passive Cutaneous Anaphylaxis; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D051966:Phospholipase C gamma; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000276:immunology; D010738:Type C Phospholipases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D002413:Cations, Divalent; D016207:Cytokines; D007527:Isoenzymes; D017455:Receptors, IgE; D017452:Receptors, IgG; D007073:Immunoglobulin E; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium