Mast cell degranulation and de novo cytokine production is a consequence of antigen-aggregation of the immunoglobulin E (IgE)-occupied high affinity receptor for IgE (FcεRI). Herein, we report that lymphokines that promote allergic inflammation, like MCP-1, were potently induced at low antigen (Ag) concentrations or at low receptor occupancy with IgE whereas some that down-regulate this response, like interleukin (IL)-10, required high receptor occupancy. Weak stimulation of mast cells caused minimal degranulation whereas a half-maximal secretory response was observed for chemokines and, with the exception of TNF-α, a weaker cytokine secretory response was observed. The medium from weakly stimulated mast cells elicited a monocyte/macrophage chemotactic response similar to that observed at high receptor occupancy. Weak stimulation also favored the phosphorylation of Gab2 and p38MAPK, while LAT and ERK2 phosphorylation was induced by a stronger stimulus. Gab2-deficient mast cells were severely impaired in chemokine mRNA induction whereas LAT-deficient mast cells showed a more pronounced defect in cytokines. These findings demonstrate that perturbation of small numbers of IgE receptors on mast cells favors certain signals that contribute to a lymphokine response that can mediate allergic inflammation.
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2 June 2003
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June 02 2003
Preferential Signaling and Induction of Allergy-promoting Lymphokines Upon Weak Stimulation of the High Affinity IgE Receptor on Mast Cells
Claudia Gonzalez-Espinosa,
Claudia Gonzalez-Espinosa
1Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
2Pharmacobiology Department, CINVESTAV Zona Sur, Calzada de los Tenorios 235, Mexico D.F., CP 14330 Mexico
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Sandra Odom,
Sandra Odom
1Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
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Ana Olivera,
Ana Olivera
1Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
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J. Peyton Hobson,
J. Peyton Hobson
3Department of Biochemistry, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298
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Maria Eugenia Cid Martinez,
Maria Eugenia Cid Martinez
2Pharmacobiology Department, CINVESTAV Zona Sur, Calzada de los Tenorios 235, Mexico D.F., CP 14330 Mexico
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Antonio Oliveira-dos-Santos,
Antonio Oliveira-dos-Santos
4Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria
5Ontario Cancer Institute, University Health Network and Departments of Medical Biophysics and Immunology, University of Toronto, M5G 2C1 Toronto, Canada
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Lillian Barra,
Lillian Barra
4Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria
5Ontario Cancer Institute, University Health Network and Departments of Medical Biophysics and Immunology, University of Toronto, M5G 2C1 Toronto, Canada
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Sarah Spiegel,
Sarah Spiegel
3Department of Biochemistry, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298
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Josef M. Penninger,
Josef M. Penninger
4Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria
5Ontario Cancer Institute, University Health Network and Departments of Medical Biophysics and Immunology, University of Toronto, M5G 2C1 Toronto, Canada
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Juan Rivera
Juan Rivera
1Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
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Claudia Gonzalez-Espinosa
1Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
2Pharmacobiology Department, CINVESTAV Zona Sur, Calzada de los Tenorios 235, Mexico D.F., CP 14330 Mexico
Sandra Odom
1Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
Ana Olivera
1Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
J. Peyton Hobson
3Department of Biochemistry, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298
Maria Eugenia Cid Martinez
2Pharmacobiology Department, CINVESTAV Zona Sur, Calzada de los Tenorios 235, Mexico D.F., CP 14330 Mexico
Antonio Oliveira-dos-Santos
4Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria
5Ontario Cancer Institute, University Health Network and Departments of Medical Biophysics and Immunology, University of Toronto, M5G 2C1 Toronto, Canada
Lillian Barra
4Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria
5Ontario Cancer Institute, University Health Network and Departments of Medical Biophysics and Immunology, University of Toronto, M5G 2C1 Toronto, Canada
Sarah Spiegel
3Department of Biochemistry, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298
Josef M. Penninger
4Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria
5Ontario Cancer Institute, University Health Network and Departments of Medical Biophysics and Immunology, University of Toronto, M5G 2C1 Toronto, Canada
Juan Rivera
1Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
Address correspondence to Juan Rivera, NIAMS/NIH, Building 10, Room 9N228, Bethesda, MD 20892-1820. Phone: 301-496-7592; Fax: 301-480-1580; E-mail: [email protected]
*
Abbreviations used in this paper: BMMC, bone marrow–derived mast cell; MCP-1, monocyte chemoattractant protein 1; MIP1α, macrophage inflammatory protein 1α; RPA, ribonuclease protection assay.
Received:
October 14 2002
Revision Received:
March 23 2003
Accepted:
March 23 2003
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 197 (11): 1453–1465.
Article history
Received:
October 14 2002
Revision Received:
March 23 2003
Accepted:
March 23 2003
Citation
Claudia Gonzalez-Espinosa, Sandra Odom, Ana Olivera, J. Peyton Hobson, Maria Eugenia Cid Martinez, Antonio Oliveira-dos-Santos, Lillian Barra, Sarah Spiegel, Josef M. Penninger, Juan Rivera; Preferential Signaling and Induction of Allergy-promoting Lymphokines Upon Weak Stimulation of the High Affinity IgE Receptor on Mast Cells . J Exp Med 2 June 2003; 197 (11): 1453–1465. doi: https://doi.org/10.1084/jem.20021806
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