title: 1-Fluoro-2,4-dinitrobenzene and its derivatives act as secretagogues on rodent mast cells.
abstract: Accumulating evidence suggests that activated mast cells are involved in contact hypersensitivity, although the precise mechanisms of their activation are still not completely understood. We investigated the potential of common experimental allergens to induce mast cell activation using murine bone marrow-derived cultured mast cells and rat peritoneal mast cells. Among these allergens, 1-chloro-2,4-dinitrobenzene and 1-fluoro-2,4-dinirobenzene (DNFB) were found to induce degranulation of rat peritoneal mast cells. DNFB-induced degranulation is accompanied by cytosolic Ca2+mobilization and is significantly inhibited by pertussis toxin, U73122 (a phospholipase C inhibitor), and BAPTA (a Ca2+chelator), raising the possibility that DNFB acts on the G protein-coupled receptors and activates Gi, which induces activation of phospholipase C, as well as known mast cell secretagogues, such as compound 48/80. DNFB could induce mast cell degranulation in the absence of serum proteins and IgE. Structure-activity relationship analyses revealed an inverse correlation between the degree of degranulation and the electron density of the C1 carbon of the DNFB derivatives. These findings raise a possibility that DNFB functions as a potent contact allergen through induction of cutaneous mast cell degranulation.
authors.affiliation: Department of Immunobiology, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Manabe
authors.affiliation: Department of Immunobiology, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Marie
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: Department of Immunobiology, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Sakamaki
authors.affiliation: Department of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Inoue
authors.affiliation: Department of Immunobiology, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kakinoki
authors.affiliation: Department of Immunobiology, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hokari
authors.affiliation: Department of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Hyogo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Sakanaka
authors.affiliation: Department of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.affiliation: Lead Exploration Unit, Drug Discovery Initiative, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyachi
authors.affiliation: Department of Immunobiology, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Furuta
authors.affiliation: Department of Immunobiology, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives / Q000737:chemistry / Q000276:immunology*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D011485:Protein Binding; D055503:Protein Multimerization; D051381:Rats; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines; D004139:Dinitrofluorobenzene; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium
keywords: 1-Fluoro-2,4-dinitrobenzene; Contact hypersensitivity; Histamine; Inflammation; Mast cells