title: Suppression of eosinophilic airway inflammation by treatment with alpha-galactosylceramide.
abstract: To clarify the essential role of NKT cells in allergy, we investigated the contribution of NKT cells to the pathogenesis of eosinophilic airway inflammation using alpha-galactosylceramide (alpha-GalCer), a selective ligand for NKT cells. Although continuous administration of alpha-GalCer during ovalbumin (OVA) sensitization increased OVA-specific IgE levels and worsened eosinophil inflammation, a single administration of alpha-GalCer at the time of OVA challenge completely prevented eosinophilic infiltration in wild-type mice. This inhibitory effect of alpha-GalCer was associated with a decrease in airway hyperresponsiveness, an increase in IFN-gamma, and decreases in IL-4, IL-5 and IL-13 levels in the bronchoalveolar lavage fluids. Analysis of lung lymphocytes revealed that production of IFN-gamma increased in NK cells, but not in T or NKT cells, following alpha-GalCer administration. Induction of vascular cell adhesion molecule-1 in the lungs of wild-type mice was also significantly attenuated by treatment with alpha-GalCer. These effects of alpha-GalCer were abrogated in J alpha281-/- mice, which lack NKT cells, and in wild-type mice treated with anti-IFN-gamma Ab. Hence, our data indicate that alpha-GalCer suppresses allergen-induced eosinophilic airway inflammation, possibly by inducing a Th1 bias that results in inhibition of eosinophil adhesion to the lung vessels.
authors.affiliation: Department of Pulmonary Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. mk01a231@md.tsukuba.ac.jp
authors.forename: Yuko
authors.initials: Y
authors.lastname: Morishima
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ishii
authors.forename: Toru
authors.initials: T
authors.lastname: Kimura
authors.forename: Akira
authors.initials: A
authors.lastname: Shibuya
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shibuya
authors.forename: Ahmed E
authors.initials: AE
authors.lastname: Hegab
authors.forename: Takashi
authors.initials: T
authors.lastname: Iizuka
authors.forename: Takumi
authors.initials: T
authors.lastname: Kiwamoto
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsuno
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nomura
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Kiyohisa
authors.initials: K
authors.lastname: Sekizawa
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D024042:Collagen Type I / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000187:drug effects / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology
chemical_list: D024042:Collagen Type I; D005699:Galactosylceramides; D018793:Interleukin-13; D015848:Interleukin-5; D019010:Vascular Cell Adhesion Molecule-1; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin