title: Effect of radiographic contrast media on histamine release from human mast cells and basophils.
abstract: Radiographic contrast media (RCM) cause histamine-dependent allergic-like reactions. The direct effects of diatrizoate (high osmolar ionic monomer), ioxaglate (low osmolar ionic dimer), iopromide (low osmolar non ionic monomer) and iotrolan (iso-osmolar non ionic dimer) at the concentration of 200 mgI ml-1 (60 min exposure) on the release of histamine from human basophils, human lung mast cells (HLMC), and human skin mast cells (HSMC) were investigated. Diatrizoate induced 48 +/- 4% histamine release in basophils, 15 +/- 3% in HLMC and 25 +/- 6% in HSMC. The remaining RCM were relatively ineffective activators of histamine release in both HLMC and HSMC (ioxaglate 4 +/- 1% and 4 +/- 1%, iopromide 5 +/- 1% and 7 +/- 2%, iotrolan 7 +/- 2% and 10 +/- 3%, respectively). Both iotrolan and ioxaglate were effective in basophils inducing 21 +/- 3% and 24 +/- 6% histamine release, respectively, whereas iopromide was relatively ineffective (7 +/- 4%). Diatrizoate induced histamine release from all three cell types with optimal levels of histamine release after a 2-4 h incubation although significant levels occurred within 15 min. Dose-dependent histamine release from HLMC occurred in all four types of RCM, the largest response (37 +/- 3%) being produced by diatrizoate. The effect of osmolality on histamine release was investigated using different concentrations of mannitol solutions (0.25, 0.5 and 1 M). Histamine release from HLMC, HSMC and basophils after 90 min exposure to mannitol (1 M) was 24 +/- 2% (p < 0.05), 9 +/- 3% (p = 0.06) and 49 +/- 1% (p < 0.05), respectively, suggesting that hyperosmolality per se can induce histamine release from basophils and mast cells. Diatrizoate-induced histamine release in all three cell types was significantly reduced by lowering the temperature to 0 degree C and partially attenuated by the metabolic inhibitors antimycin A (1 microM) and 2-deoxyglucose (5 mM), and by the omission of glucose from the buffer solution. Diatrizoate-induced histamine release was not dependent on extracellular calcium. These data suggest that diatrizoate induces histamine release at least in part by non-cytotoxic mechanisms.
authors.affiliation: Department of Medicine and Pharmacology, Sheffield University, Royal Hallamshire Hospital, UK.
authors.forename: P T
authors.initials: PT
authors.lastname: Peachell
authors.forename: S K
authors.initials: SK
authors.lastname: Morcos
mesh_terms: D001491:Basophils / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D018929:Cell Culture Techniques; D003287:Contrast Media / Q000494:pharmacology*; D003973:Diatrizoate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007223:Infant; D008168:Lung / Q000166:cytology; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D009994:Osmolar Concentration; D013696:Temperature; D013997:Time Factors
chemical_list: D003287:Contrast Media; D003973:Diatrizoate; D002118:Calcium