title: Preferential signaling and induction of allergy-promoting lymphokines upon weak stimulation of the high affinity IgE receptor on mast cells.
abstract: 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 (Fc epsilon RI). 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-alpha, 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.
authors.affiliation: Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gonzalez-Espinosa
authors.forename: Sandra
authors.initials: S
authors.lastname: Odom
authors.forename: Ana
authors.initials: A
authors.lastname: Olivera
authors.forename: J Peyton
authors.initials: JP
authors.lastname: Hobson
authors.forename: Maria Eugenia Cid
authors.initials: ME
authors.lastname: Martinez
authors.forename: Antonio
authors.initials: A
authors.lastname: Oliveira-Dos-Santos
authors.forename: Lillian
authors.initials: L
authors.lastname: Barra
authors.forename: Sarah
authors.initials: S
authors.lastname: Spiegel
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.forename: Juan
authors.initials: J
authors.lastname: Rivera
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D015550:Cell Degranulation / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006967:Hypersensitivity / Q000209:etiology / Q000235:genetics / Q000276:immunology; D007073:Immunoglobulin E / Q000378:metabolism; D066298:In Vitro Techniques; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000941:Antigens; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D008222:Lymphokines; D012333:RNA, Messenger; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases