Stellato C, de Crescenzo G, Patella V, Mastronardi P, Mazzarella B, Marone G
Division of Clinical Immunology, School of Medicine, University of Naples Federico II, Italy.
J Allergy Clin Immunol. 1996 Mar;97(3):838-50. doi: 10.1016/s0091-6749(96)80162-x.
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.
嗜碱性粒细胞和肥大细胞的激活在碘化放射性造影剂给药期间发生的类过敏反应的发病机制中起作用。
我们比较了三种造影剂(CM),即碘克沙醇(碘克沙酸的钠和葡甲胺盐)、碘他拉醇(碘他拉酸的钠和葡甲胺盐)和碘海醇(碘佛醇)对从肺、皮肤和心脏组织分离的人嗜碱性粒细胞和肥大细胞中预先形成的介质(组胺和类胰蛋白酶)以及新合成的介质(前列腺素D2和白三烯C4)释放的影响。对市售制剂与纯物质进行了平行评估。甘露醇用作通过高渗刺激诱导组胺释放(HR)的阳性对照。
碘克沙醇(0.1至0.3mol/L)、碘他拉醇(0.1至0.5mol/L)、碘海醇(0.2至0.5mol/L)以及相应的纯物质浓度依赖性地诱导嗜碱性粒细胞释放HR。发现CM渗透压与嗜碱性粒细胞的HR之间存在正相关。从不同解剖部位分离的肥大细胞对三种CM的反应不同。碘克沙醇和碘海醇诱导人肺肥大细胞释放组胺和类胰蛋白酶,但不诱导人皮肤肥大细胞释放。CM渗透压与来自人肺肥大细胞的HR之间未发现相关性。CM诱导人肺肥大细胞释放组胺和类胰蛋白酶的百分比之间存在显著相关性。碘克沙醇、碘他拉醇和碘海醇也诱导人心脏肥大细胞释放组胺和类胰蛋白酶。没有一种CM诱导嗜碱性粒细胞或肥大细胞从头合成白三烯C4或前列腺素D2。CM引起的HR动力学根据所用药物和所检查的细胞(嗜碱性粒细胞或人肺肥大细胞)而有所不同。CM诱导嗜碱性粒细胞和人肺肥大细胞释放HR是温度依赖性的,部分受细胞外Ca2+浓度影响,并且嗜碱性粒细胞与IL-2或IL-3预孵育不会改变这种情况。
这些结果提供了证据,证明CM对来自不同解剖部位的人嗜碱性粒细胞和肥大细胞介质释放的影响具有异质性。它们还表明高渗可能是CM激活嗜碱性粒细胞的一个重要因素,但对肥大细胞的相关性较小。CM仅诱导预先形成的介质释放。血浆类胰蛋白酶的测量可能在临床上有助于监测由CM引起的不良反应。