title: Treatment of murine mast cells with IgEκ and protein L enhances apoptotic cell death induced by IL-3 withdrawal.
abstract: Engagement of the high-affinity IgE receptor (FcεRI) can be either protective or non-protective against apoptotic cell death (ACD) in bone marrow-derived murine mast cells (BMMCs) after IL-3 withdrawal, depending on the avidity between IgE and its antigen. We recently reported that protein L (PpL), a bacterial Igκ-binding soluble protein, is able to stimulate intracellular signaling to induce activation of BMMCs by interacting with the IgEκ-FcεRI complex. However, it is unclear if cross-linking of FcεRI with IgEκ and PpL prevents or enhances IL-3-dependent ACD in BMMCs. In the present study, we found that IL-3-dependent ACD of BMMCs is accelerated by loading soluble PpL in the presence of IgEκ-occupied FcεRIα. For this purpose, soluble PpL was incorporated into the BMMCs. Unlike soluble PpL, immobilized PpL failed to enhance ACD, although both forms of PpL induced IL-6 production equally in BMMCs. In addition, we observed that DNS5-BSA protected anti-DNS IgE-sensitized BMMCs from IL-3 depletion-mediated ACD by inducing the production of autocrine IL-3. In contrast, DNS5-PpL enhanced IL-3 withdrawal-induced ACD of anti-DNS IgE-sensitized BMMCs and reduced the production of autocrine IL-3. These findings suggest that PpL increases IL-3 withdrawal-induced ACD of IgEκ-sensitized BMMCs by incorporating PpL into the BMMCs and that this internalized PpL may interfere with survival signals via FcεRI.
authors.affiliation: Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan; Allergy and Immunology Group, Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan. Electronic address: nunomura.satoshi@nihon-u.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nunomura
authors.affiliation: Allergy and Immunology Group, Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Okayama
authors.affiliation: Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Terui
authors.affiliation: Allergy and Immunology Group, Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan; Department of Microbiology, Nihon University School of Medicine, Tokyo, Japan; Asahi Hospital, Chiba, Japan.
authors.forename: Chisei
authors.initials: C
authors.lastname: Ra
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology* / Q000494:pharmacology; D002478:Cells, Cultured; D055767:Immobilized Proteins / Q000276:immunology / Q000494:pharmacology; D007073:Immunoglobulin E / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000276:immunology*; D007377:Interleukin-3 / Q000276:immunology*; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017455:Receptors, IgE / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; C055047:Ig L-binding protein, Peptostreptococcus; D055767:Immobilized Proteins; D007145:Immunoglobulin kappa-Chains; D007377:Interleukin-3; D017455:Receptors, IgE; D007073:Immunoglobulin E
keywords: Cell death; IgE receptor; Mast cells; Protein L; Superantigen