Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcepsilonRI.
We demonstrate that binding of different IgE molecules (IgEs) to their receptor, FcepsilonRI, induces a spectrum of activation events in the absence of a specific antigen and provide evidence that such activation reflects aggregation of FcepsilonRI. Highly cytokinergic IgEs can efficiently induce production of cytokines and render mast cells resistant to apoptosis in an autocrine fashion, whereas poorly cytokinergic IgEs induce these effects inefficiently. Highly cytokinergic IgEs seem to induce more extensive FcepsilonRI aggregation than do poorly cytokinergic IgEs, which leads to stronger mast cell activation and survival effects. These effects of both types of IgEs require Syk tyrosine kinase and can be inhibited by FcepsilonRI disaggregation with monovalent hapten. In hybridoma-transplanted mice, mucosal mast cell numbers correlate with serum IgE levels. Therefore, survival effects of IgE could contribute to the pathogenesis of allergic disease.
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.
Jiro
J
Kitaura
Jinming
J
Song
Mindy
M
Tsai
Koichi
K
Asai
Mari
M
Maeda-Yamamoto
Attila
A
Mocsai
Yuko
Y
Kawakami
Fu-Tong
FT
Liu
Clifford A
CA
Lowell
B George
BG
Barisas
Stephen J
SJ
Galli
Toshiaki
T
Kawakami
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D017930:Genes, Reporter; D006632:Histamine / Q000378:metabolism; D006825:Hybridomas / Q000637:transplantation; D007073:Immunoglobulin E / Q000276:immunology*; D007377:Interleukin-3 / Q000494:pharmacology; D015289:Leukotrienes / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D017455:Receptors, IgE / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic; D014184:Transplantation, Homologous / Q000276:immunology
D016207:Cytokines; D007377:Interleukin-3; D015289:Leukotrienes; D017455:Receptors, IgE; D007073:Immunoglobulin E; D006632:Histamine; D008156:Luciferases