title: The quantity and duration of FcRgamma signals determine mast cell degranulation and survival.
abstract: Immunoglobulin E (IgE) bound to multivalent antigen (Ag) elicits mast cell degranulation but not survival; on the contrary, IgE in the absence of Ag (IgE(-Ag)) induces survival only but not degranulation. Although these distinct responses are mediated through the same receptor, FcepsilonRI, the molecular mechanism generating the divergence is largely unknown. We recently showed that the signals through FcRgamma chain are essential for IgE(-Ag)-induced mast cell survival as well as IgE(+Ag)-induced degranulation. To determine whether the cellular output is regulated by the quantity of FcRgamma signal, we expressed CD8/FcRgamma chimeras (CD8/gamma) in bone marrow-derived mast cells (BMMCs) from FcRgamma(-/-) mice to manipulate the strength of FcRgamma signals by anti-CD8 cross-linking. Cross-linking of CD8/gamma induced mast cell survival and degranulation. Survival was induced by weaker stimulation than needed for degranulation in terms of anti-CD8 concentration and the valency of chimera. However, sustained extracellular signal-regulated kinase (Erk) activation seems to regulate survival even when the activation signal was strong enough to elicit degranulation. Generation of sustained Erk activation by active mitogen-activated protein kinase kinase (MEK) induced BMMC survival. These results suggest that the duration and the magnitude of FcRgamma signals may determine mast cell survival and degranulation, respectively.
authors.affiliation: Department of Molecular Genetics (H1), Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Eri
authors.initials: E
authors.lastname: Ishikawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kohno
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism; D015550:Cell Degranulation; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis; D004789:Enzyme Activation; D007073:Immunoglobulin E / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology*; D021962:Membrane Microdomains / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016827:CD8 Antigens; D016207:Cytokines; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E; D020928:Mitogen-Activated Protein Kinases