Human basophil/mast cell releasability. XI. Heterogeneity of the effects of contrast media on mediator release

Abstract

The activation of basophils and mast cells plays a role in the pathogenesis of anaphylactoid reactions occurring during the administration of iodinated radiocontrast media. We compared the effects of three contrast media (CM), Hexabrix (sodium and meglumine salts of ioxaglic acid), Telebrix (sodium and meglumine salts of ioxitalamic acid), and Optiray (ioversol) on the release of preformed (histamine and tryptase) and de novo synthesized (prostaglandin D2 and leukotriene C4) mediators from human basophils and mast cells isolated from lung, skin, and heart tissue. The commercial preparations were evaluated in parallel with the pure substances. Mannitol was used as a positive control inducing histamine release (HR) by hyperosmolar stimulation. Hexabrix (0.1 to 0.3 mol/L), Telebrix (0.1 to 0.5 mol/L), Optiray (0.2 to 0.5 mol/L), and the corresponding pure substances concentration-dependently induced HR from basophils. A positive correlation was found between CM osmolality and HR from basophils. Mast cells isolated from different anatomic sites responded differently to the three CM. Hexabrix and Optiray induced histamine and tryptase release from human lung mast cells, but not from human skin mast cells. No correlation was found between the osmolality of CM and HR from human lung mast cells. There was a significant correlation between the percent of histamine and tryptase release induced by CM from human lung mast cells. Hexabrix, Telebrix, and Optiray also induced histamine and tryptase release from human heart mast cells. None of the CM induced the de novo synthesis of leukotriene C4 or prostaglandin D2 from basophils or mast cells. The kinetics of HR caused by CM differed according to the drug used and the cell (basophils or human lung mast cells) examined. CM-induced HR from basophils and human lung mast cells was temperature-dependent, partially influenced by extracellular Ca2+ concentrations, and not modified by preincubation of basophils with IL-2 or IL-3. These results provide evidence of the heterogeneity of the effects of CM on mediator release from human basophils and mast cells from different anatomic sites. They also suggest that hyperosmolarity may be an important factor in the activation of basophils by CM, but less relevant for mast cells. CM induce only the release of preformed mediators. The measurement of plasma tryptase might be clinically useful for monitoring adverse reactions caused by CM.