title: Stem cell factor programs the mast cell activation phenotype.
abstract: Mast cells, activated by Ag via FcεRI, release an array of proinflammatory mediators that contribute to allergic disorders, such as asthma and anaphylaxis. The KIT ligand, stem cell factor (SCF), is critical for mast cell expansion, differentiation, and survival, and under acute conditions, it enhances mast cell activation. However, extended SCF exposure in vivo conversely protects against fatal Ag-mediated anaphylaxis. In investigating this dichotomy, we identified a novel mode of regulation of the mast cell activation phenotype through SCF-mediated programming. We found that mouse bone marrow-derived mast cells chronically exposed to SCF displayed a marked attenuation of FcεRI-mediated degranulation and cytokine production. The hyporesponsive phenotype was not a consequence of altered signals regulating calcium flux or protein kinase C, but of ineffective cytoskeletal reorganization with evidence implicating a downregulation of expression of the Src kinase Hck. Collectively, these findings demonstrate a major role for SCF in the homeostatic control of mast cell activation with potential relevance to mast cell-driven disease and the development of novel approaches for the treatment of allergic disorders.
authors.affiliation: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Ito
authors.forename: Daniel
authors.initials: D
authors.lastname: Smrž
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Jung
authors.forename: Geethani
authors.initials: G
authors.lastname: Bandara
authors.forename: Avanti
authors.initials: A
authors.lastname: Desai
authors.forename: Šárka
authors.initials: Š
authors.lastname: Smržová
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Kuehn
authors.forename: Michael A
authors.initials: MA
authors.lastname: Beaven
authors.forename: Dean D
authors.initials: DD
authors.lastname: Metcalfe
authors.forename: Alasdair M
authors.initials: AM
authors.lastname: Gilfillan
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D006706:Homeostasis / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016130:Immunophenotyping; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D019089:Stem Cell Factor / Q000502:physiology*
chemical_list: D019089:Stem Cell Factor