title: Role of mast cells and basophils in IgE responses and in allergic airway hyperresponsiveness.
abstract: We established a diphtheria toxin (DT)-based conditional deletion system using Il4 enhancer elements previously shown to be specific for IL-4 production in mast cells (MCs) or basophils (Mas-TRECK and Bas-TRECK mice). DT treatment of Bas-TRECK mice resulted in specific deletion of basophils, whereas both MCs and basophils were deleted in Mas-TRECK mice. DT-treated Mas-TRECK mice had impaired passive cutaneous anaphylaxis, IgE-mediated passive systemic anaphylaxis, and IgE-mediated chronic allergic inflammation, whereas DT-treated Bas-TRECK mice had impaired IgE-mediated chronic allergic inflammation. Using these mice, we also sought to tease out the role of MCs and basophils in airway hyperresponsiveness (AHR). Although MC deletion resulted in a slight increase in basal Ag-specific IgE levels and significant increases in basal IgE levels, we found that this deletion markedly impaired the AHR effector phase and was accompanied by decreased histamine levels. By contrast, basophil deletion had no effect on the AHR effector phase or on IgE production induced by systemic OVA immunization. Our results, using these newly established Mas-TRECK and Bas-TRECK models, demonstrated an indispensable role for MCs as effector cells in AHR.
authors.affiliation: Research Center for Allergy and Immunology, RIKEN, Yokohama Institute, Kanagawa 230-0045, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Sawaguchi
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Harada
authors.forename: Kaori
authors.initials: K
authors.lastname: Mukai
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishiwata
authors.forename: Keisuke
authors.initials: K
authors.lastname: Oboki
authors.forename: Taku
authors.initials: T
authors.lastname: Kambayashi
authors.forename: Naohiro
authors.initials: N
authors.lastname: Watanabe
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Inoue
authors.forename: Masato
authors.initials: M
authors.lastname: Kubo
mesh_terms: D000818:Animals; D001491:Basophils / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D004167:Diphtheria Toxin / Q000494:pharmacology; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology*
chemical_list: D004167:Diphtheria Toxin; D015847:Interleukin-4; D007073:Immunoglobulin E