title: IgE and IgA produced by OX40-OX40L or CD40-CD40L interaction in B cells-mast cells re-activate FcεRI or FcαRI on mast cells in mouse allergic asthma.
abstract: Mast cells are major effector cells of allergic diseases related to IgE. This study was undertaken to determine whether IgE or IgA, produced by CD40-CD40L or OX40-OX40L interactions between B cells and mast cells, re-activate FcεRI or FcαRI on mast cell surface. C57BL mice were sensitized and subjected to OVA challenge to induce asthma. Bone marrow-derived mast cells (BMMCs) and primary B cells were co-cultured. Mast cell recruitment into airways was stained by May-Grünwald Giemsa, the expression of markers or signaling molecules were determined by immunohistochemistry or Western blotting, and co-localization of B cells and mast cells by immunofluorescence. Anti-CD40 plus anti-OX40L Abs synergistically reduced IgE and IgA production, and mediators (histamine, LTs and cytokines) released in mast cells, and additively reduced other responses, such as, numbers of mast cells, the expression of markers (tryptase, mMCP5, B220 and CD19), surface molecules (CD40, CD40L, OX40 and OX40L), FcεRI or FcαRI and the co-localization of BMMCs and B cells, and IgE- or IgA-producing cells, as compared with individual blocking Ab treatment which reducedresponses in BAL cells or lung tissues of OVA-challenged mice or in co-culture of B and mast cells. The data suggest that IgE and IgA, produced by OX40-OX40L or CD40-CD40L interaction between B cells and mast cells, may re-activate receptors of FCεRI and FcαRI on mast cell surfaces, followed by more mediator release, and furthermore, that treatment with anti-CD40 plus anti-OX40L Abs offers a potential treatment for allergic asthma.
authors.affiliation: Department of Pharmacology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Department of Pharmacology, Suwon 440-746, South Korea.
authors.forename: Gwan Ui
authors.initials: GU
authors.lastname: Hong
authors.affiliation: Department of Pharmacology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Department of Pharmacology, Suwon 440-746, South Korea.
authors.forename: Ji Yeun
authors.initials: JY
authors.lastname: Lim
authors.affiliation: Department of Pharmacology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Department of Pharmacology, Suwon 440-746, South Korea.
authors.forename: Nam Goo
authors.initials: NG
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Department of Pharmacology, Suwon 440-746, South Korea.
authors.forename: Joo-Ho
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Pharmacology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Department of Pharmacology, Suwon 440-746, South Korea. Electronic address: jyro426@skku.edu.
authors.forename: Jai Youl
authors.initials: JY
authors.lastname: Ro
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006632:Histamine / Q000378:metabolism; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D008168:Lung / Q000276:immunology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D053278:OX40 Ligand / Q000276:immunology*; D011961:Receptors, Fc / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D019013:CD40 Antigens; D016207:Cytokines; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D053278:OX40 Ligand; C406562:OX40Ig; D011961:Receptors, Fc; D017455:Receptors, IgE; D023201:CD40 Ligand; D007073:Immunoglobulin E; D006632:Histamine
keywords: Aluminum hydroxide gel (PubChem CID: 6328211); Anti-CD40 Ab; Anti-OX40 Ab; B cells; Dinitrophenol (PubChem CID: 1493); IgA; IgE; Mast cells; Ovalbumin (PubChem CID: 71311993)