Fc epsilon RI gamma-ITAM is differentially required for mast cell function in vivo.
The cross-linking of IgE-bound FcepsilonRI by Ags triggers mast cell activation leading to allergic reactions. The in vivo contribution of FcepsilonRIgamma signaling to IgE/FcepsilonRI-mediated mast cell responses has not yet been elucidated. In this study FcepsilonRIgamma(-/-) mast cells were reconstituted with either wild-type or mutant FcepsilonRIgamma in transgenic mice and transfected mast cells in vitro. We demonstrate that FcepsilonRIgamma-immunoreceptor tyrosine-based activation motif is essential for degranulation, cytokine production, and PG synthesis as well as for passive systemic anaphylaxis. Recent reports have suggested that cell surface FcepsilonRI expression and mast cell survival are regulated by IgE in the absence of Ag, although the molecular mechanism is largely unknown. We also found that the promotion of mast cell survival by IgE without Ags is mediated by signals through the FcepsilonRIgamma-immunoreceptor tyrosine-based activation motif. In contrast, the IgE-mediated up-regulation of FcepsilonRI is independent of FcepsilonRIgamma signaling. These results indicate that FcepsilonRIgamma-mediated signals differentially regulate the receptor expression, activation, and survival of mast cells and systemic anaphylaxis.
Sakurai
Daiju
D
Departments of Molecular Genetics and Otorhinolaryngology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Yamasaki
Sho
S
Arase
Kanako
K
Park
Seung Yong
SY
Arase
Hisashi
H
Konno
Akiyoshi
A
Saito
Takashi
T
D020816:Amino Acid Motifs / Q000276:immunology; D000707:Anaphylaxis / Q000235:genetics / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003433:Crosses, Genetic; D003593:Cytoplasm / Q000235:genetics / Q000276:immunology; D007073:Immunoglobulin E / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017455:Receptors, IgE / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000941:Antigens; D010446:Peptide Fragments; D021122:Protein Subunits; D017455:Receptors, IgE; D007073:Immunoglobulin E