Wang X S, Lau H Y A
Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, New Territories, Hong Kong, China.
Allergy. 2006 Apr;61(4):503-6. doi: 10.1111/j.1398-9995.2006.01043.x.
Mast cells cultured from human peripheral blood have been widely used to study human mast cell function. Prostanoids are the important regulators of mast cell activity, however, there were no reports about the class of prostanoid receptors expressed on such cultured cells.
The present study was to characterize pharmacologically the prostanoid receptors by investigating the effects of prostanoid receptor agonists on the immunoglobulin E (IgE)-mediated histamine release from the cultured mast cells.
Mast cells cultured from human progenitor cells in peripheral blood were sensitized with human myeloma IgE, and then challenged with anti-human IgE following pretreatment with diverse prostanoid receptor agonists. The histamine content in supernatants and cell pellets were measured by histamine auto-analyzer.
Of the prostanoid receptor agonists tested, the prostaglandin E2 (PGE2) receptor (EP receptor) agonist PGE2 (10(-7) to 10(-11) M) produced concentration-related potentiation of IgE-mediated histamine release from the cultured mast cells. Sulprostone, an EP1/EP3 agonist, SC-46275, a selective EP3 agonist, and 11-deoxy-PGE1, a selective EP2/EP3/EP4 agonist also caused a significant increase in histamine release induced by anti-IgE. BW245C, fluprostone, cicaprost and U46619 for the prostaglandin D2, F2alpha, I2, and thromboxane A2 receptors respectively, and the EP2/EP4 receptor agonist butaprost had little effect on anti-IgE stimulated histamine release from mast cells.
The present results suggest that PGE2 potentiates the IgE-mediated histamine release from the cultured mast cell via EP3 and/or EP1 receptors.
从人外周血培养的肥大细胞已被广泛用于研究人类肥大细胞功能。前列腺素是肥大细胞活性的重要调节剂,然而,关于此类培养细胞上表达的前列腺素受体类别尚无报道。
本研究旨在通过研究前列腺素受体激动剂对培养的肥大细胞中免疫球蛋白E(IgE)介导的组胺释放的影响,从药理学角度对前列腺素受体进行表征。
用人外周血祖细胞培养的肥大细胞用人骨髓瘤IgE致敏,然后在用不同的前列腺素受体激动剂预处理后,用抗人IgE进行刺激。用组胺自动分析仪测量上清液和细胞沉淀中的组胺含量。
在所测试的前列腺素受体激动剂中,前列腺素E2(PGE2)受体(EP受体)激动剂PGE2(10⁻⁷至10⁻¹¹M)对培养的肥大细胞中IgE介导的组胺释放产生浓度相关的增强作用。EP1/EP3激动剂舒前列素、选择性EP3激动剂SC-46275以及选择性EP2/EP3/EP4激动剂11-脱氧-PGE1也导致抗IgE诱导的组胺释放显著增加。分别针对前列腺素D2、F2α、I2和血栓素A2受体的BW245C、氟前列素、西卡前列素和U46619,以及EP2/EP4受体激动剂布他前列素对肥大细胞中抗IgE刺激的组胺释放几乎没有影响。
目前的结果表明,PGE2通过EP3和/或EP1受体增强培养的肥大细胞中IgE介导的组胺释放。