title: Down-modulation of antigen-induced activation of murine cultured mast cells sensitized with a highly cytokinergic IgE clone.
abstract: Accumulating evidence suggests that several IgE clones can activate mast cells during the sensitization phase even in the absence of antigen. They were found to induce pro-inflammatory cytokine release, histamine synthesis, chemotaxis, adhesion, and accelerated maturation of mast cells, although it remains unknown whether antigen-induced responses can be affected by differences of IgE clones. We compared two IgE clones, which were different in the capacity to activate mast cells during sensitization, in terms of potentials to affect antigen-induced degranulation and cytokine releases using IL-3-dependent murine bone marrow-derived cultured mast cells (BMMCs). Antigen-induced degranulation and pro-inflammatory cytokine release were augmented, when BMMCs were sensitized with elevated concentrations of a clone IgE-3, which did not induce phosphorylation of JNK and cytokine release in the absence of antigen, whereas those were significantly rather decreased, when BMMCs were sensitized with elevated concentrations of a clone SPE-7, one of the most potent cytokinergic IgE clones, which intensively induced phosphorylation of JNK. This attenuated response with SPE-7 was accompanied by decreased tyrosine phosphorylation of the cellular proteins including Syk upon antigen stimulation. SP600125, which is known to inhibit JNK, restored the levels of antigen-induced degranulation and phosphorylation of Syk in BMMCs sensitized with higher concentrations of a clone SPE-7 when it was added before sensitization. Treatment with anisomycin, a potent activator of JNK, before IgE sensitization significantly suppressed antigen-induced degranulation. These findings suggest that differences of sensitizing IgE clones can affect antigen-induced responses and activation of JNK during sensitization might suppress antigen-induced activation of mast cells.
authors.affiliation: Department of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Hyogo 663-8179, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Sakanaka
authors.affiliation: Department of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Hyogo 663-8179, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kurimune
authors.affiliation: Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Tsushima-naka 1-1-1, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Tsushima-naka 1-1-1, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Hyodo
authors.affiliation: Department of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Hyogo 663-8179, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Natsuhara
authors.affiliation: Institute for Biosciences, Mukogawa Women's University, Koshien, Nishinomiya, Hyogo 663-8179, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ichikawa
authors.affiliation: Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Tsushima-naka 1-1-1, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Furuta
authors.affiliation: Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Tsushima-naka 1-1-1, Kita-ku, Okayama 700-8530, Japan. Electronic address: tanaka@pharm.okayama-u.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D000941:Antigens / Q000276:immunology*; D015550:Cell Degranulation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation
chemical_list: D000941:Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D007073:Immunoglobulin E; D000841:Anisomycin
keywords: Allergy; Degranulation; IgE; JNK; Mast cell