title: SHIP1 and the negative control of mast cell/basophil activation by supra-optimal antigen concentrations.
abstract: IgE-mediated, antigen-triggered activation of mast cells and basophils often results in bell-shaped dose-response curves for the release of various pro-inflammatory mediators. The degree of suppression of mediator release observed following supra-optimal stimulation varies widely for different allergens as well as for different experimental agents that cause crosslinking of high-affinity IgE receptors (FcɛRI) on these cells. While the reasons for these differences have not yet been resolved it has become increasingly apparent that supra-optimal stimulation in many cases causes a shift in the balance of stimulatory and inhibitory signal transduction mechanisms arising from FcɛRI triggering. In particular, the lipid phosphatase SHIP1 has been shown to be centrally involved in explaining the bell-shaped phenomena in both mast cells and basophils in different species and appears to play a fundamental role in limiting the IgE responsiveness of these allergic effector cells. Elucidating the nature of this inhibitory signaling pathway may provide crucial knowledge in order to optimize desensitization strategies in the treatment of allergic diseases.
authors.affiliation: Institute of Biochemistry and Molecular Immunology, RWTH Aachen University, University Clinic, Aachen, Germany. Electronic address: mhuber@ukaachen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Huber
authors.affiliation: Medway School of Pharmacy, University of Kent, Central Avenue, Chatham Maritime, Kent, United Kingdom.
authors.forename: Bernhard F
authors.initials: BF
authors.lastname: Gibbs
mesh_terms: D000818:Animals; D000941:Antigens / Q000097:blood / Q000276:immunology*; D001491:Basophils / Q000276:immunology*; D015550:Cell Degranulation / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood / Q000276:immunology; D000072181:Inositol Polyphosphate 5-Phosphatases; D008407:Mast Cells / Q000276:immunology*; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000276:immunology*; D017455:Receptors, IgE / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000941:Antigens; D018836:Inflammation Mediators; D017455:Receptors, IgE; D007073:Immunoglobulin E; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606430:INPP5D protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
keywords: Allergy; Basophil; Lipid phosphatase; Mast cell; Signal transduction