1‐Fluoro‐2,4‐dinitrobenzene and its derivatives act as secretagogues on rodent mast cells

• Published in: European journal of immunology 2017-01, Vol.47 (1), p.60-67
• Main Authors: Manabe, Yohei, Yoshimura, Marie, Sakamaki, Kazuma, Inoue, Asuka, Kakinoki, Aya, Hokari, Satoshi, Sakanaka, Mariko, Aoki, Junken, Miyachi, Hiroyuki, Furuta, Kazuyuki, Tanaka, Satoshi
• Format: Article
• Language: English
• Subjects: 1-Chloro-2,4-dinitrobenzene; 1‐Fluoro‐2,4‐dinitrobenzene; Allergens; Allergens - chemistry; Allergens - immunology; Allergies; Animals; Bone marrow; Calcium - metabolism; Calcium ions; Calcium mobilization; Cell activation; Cell Degranulation - immunology; Compound 48/80; Contact dermatitis; Contact hypersensitivity; Cytokines - metabolism; Degranulation; Dinitrobenzene; Dinitrofluorobenzene; Dinitrofluorobenzene - analogs & derivatives; Dinitrofluorobenzene - chemistry; Dinitrofluorobenzene - immunology; G protein-coupled receptors; GTP-Binding Proteins - chemistry; GTP-Binding Proteins - metabolism; Histamine; Hypersensitivity; Immunoglobulin E; Inflammation; Male; Mast cells; Mast Cells - immunology; Mast Cells - secretion; Mice; Molecular Structure; Peritoneum; Pertussis; Pertussis toxin; Phospholipase; Phospholipase C; Protein Binding; Protein Multimerization; Proteins; Rats; Rodents; Serum proteins; Signal Transduction; Type C Phospholipases - metabolism
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201646536

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. An experimental contact allergen, 1‐fluoro‐2,4‐dinitrobenzene (DNFB) directly induces cytosolic Ca2+ mobilization and degranulation in rat peritoneal mast cells. This response is sensitive to pertussis toxin and a phospholipase C inhibitor, raising the possibility that DNFB can act on the surface G protein‐coupled receptors in mast cells.