Rat basophilic leukemia (RBL 2H3) cells were passively sensitized by exposure to monoclonal anti-trinitrophenol mouse immunoglobulin E (anti-trinitrophenol IgE) (0.5 microgram/ml) and triggered by exposure to a sub-optimal concentration of trinitrophenol ovalbumin conjugate (5 ng/ml). At this concentration, trinitrophenol-ovalbumin increased histamine release from a basal rate of 4.8 +/- 0.5 to 28.5 +/- 4.6% and peptidoleukotrienes from less than 0.1 to 4.2 +/- 1.3 ng/10(6) cells in the activated cells. Ro 19-3704 and Ro 19-1400, platelet activating factor (PAF) antagonists which are structural analogs of PAF, potently inhibited both the IgE-dependent release of histamine (IC50 values of 3.0 and 3.6 microM, respectively) and LT release (IC50 values of 5.0 microM for both compounds) from the cells. These effects appeared to be independent to the ability of the compounds to act as PAF antagonists since PAF on its own had no effect on mediator release, and WEB 2086 and BN 52021, structurally distinct PAF antagonists, were relatively ineffective as inhibitors of mediator release. Ro 19-3704 and Ro 19-1400 were observed to be potent inhibitors of the soluble phospholipase A2 activity in synovial fluid from rheumatoid arthritic patients (IC50 values of 6.5 and 8.4 microM, respectively). In contrast, WEB 2086 and BN 52021 had no effect on this phospholipase A2. Ro 19-3704 significantly inhibited the IgE-dependent formation of inositol phosphates in RBL 2H3 cells (IC50 value of 7.0 microM). These data suggest that the mediator release inhibitory action of these compounds may be related to the ability of these compounds to inhibit phospholipase A2 and/or phospholipase C.

译文

:暴露于单克隆抗三硝基苯酚小鼠免疫球蛋白E(抗三硝基苯酚IgE)(0.5微克/毫升)可以被动致敏大鼠嗜碱性粒细胞白血病(RBL 2H3)细胞,并通过暴露于次适量浓度的三硝基苯酚卵白蛋白缀合物(5 ng / ml)。在此浓度下,三硝基苯酚-卵清蛋白将组胺释放从基础速率的4.8 /-0.5增加到28.5 /-4.6%,而肽白三烯从少于0.1到4.2 /-1.3 ng / 10(6)细胞增加。 Ro 19-3704和Ro 19-1400,血小板活化因子(PAF)拮抗剂,是PAF的结构类似物,可有效抑制IgE依赖的组胺释放(IC50分别为3.0和3.6 microM)和LT释放(IC50)。两种化合物的浓度值均为5.0 microM)。这些作用似乎与化合物充当PAF拮抗剂的能力无关,因为PAF本身对介质释放没有影响,并且结构不同的PAF拮抗剂WEB 2086和BN 52021作为介质释放抑制剂相对无效。观察到Ro 19-3704和Ro 19-1400是类风湿关节炎患者滑液中可溶性磷脂酶A2活性的有效抑制剂(IC50值分别为6.5和8.4 microM)。相反,WEB 2086和BN 52021对这种磷脂酶A2没有影响。 Ro 19-3704显着抑制RBL 2H3细胞中IgE依赖性肌醇磷酸的形成(IC50值为7.0 microM)。这些数据表明这些化合物的介质释放抑制作用可能与这些化合物抑制磷脂酶A2和/或磷脂酶C的能力有关。

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