title: Induction of mast cell sensitization by chemical allergens: a comparative study.
abstract: In previous investigations we have shown that chemical allergens of different classes induce in mice qualitatively divergent immune responses. Respiratory allergens provoke substantial increases in total serum concentration of IgE. In contrast, contact allergens which are known or suspected not to cause respiratory sensitization or which at most have only a very limited potential to do so, have little or no effect on total serum IgE. Such differences, we propose, provide a novel approach for the prospective identification of chemicals with potential to cause respiratory allergy. In the absence of a robust method for the direct measurement of respiratory hypersensitivity reactions in mice we have sought in the present study to determine whether the IgE responses induced in mice by respiratory allergens are specific and of sufficient magnitude to cause the active sensitization of mast cells in vivo, a prerequisite for immediate hypersensitivity, including acute-onset respiratory hypersensitivity. Topical exposure of BALB/c mice to concentrations of > or = 10% of the human respiratory allergen trimellitic anhydride (TMA) caused the specific sensitization of peritoneal mast cells in situ as measured by the conjugate-induced release of [3H]-5-hydroxytryptamine in vitro. Experiments were performed also with 2,4-dinitrochlorobenzene (DNCB), a contact allergen that fails to induce respiratory hypersensitivity. Treatment of mice with concentrations of DNCB of comparable immunogenicity failed to cause mast cell sensitization. These data demonstrate that a known human chemical respiratory allergen induces in mice specific mast-cell-sensitizing IgE antibody and reinforce the value of the mouse as a model for the evaluation of respiratory sensitization potential.
authors: Department of Pharmacology and Therapeutics, University of Liverpool, UK.
authors: M R
authors: MR
authors: Holliday
authors: J W
authors: JW
authors: Coleman
authors: R J
authors: RJ
authors: Dearman
authors: I
authors: I
authors: Kimber
mesh_terms: D000485:Allergens / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004137:Dinitrochlorobenzene / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D006241:Haptens / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010529:Peritoneal Cavity / Q000166:cytology; D010796:Phthalic Anhydrides / Q000493:pharmacokinetics / Q000633:toxicity*; D012701:Serotonin / Q000378:metabolism*
chemical_list: D000485:Allergens; D004137:Dinitrochlorobenzene; D006241:Haptens; D007074:Immunoglobulin G; D010796:Phthalic Anhydrides; D012701:Serotonin; D007073:Immunoglobulin E; C015559:trimellitic anhydride