Shishikura Takashi, Shito Keiko, Uchida Mitsuhiro, Inaba Tsuneyoshi
Pharmaceutical Research Department, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
J Pharmacol Sci. 2006 Aug;101(4):350-5. doi: 10.1254/jphs.fp0060519. Epub 2006 Aug 5.
We established a new and facile model to investigate allergic mechanism and assess the effect of antiallergic compounds. Male Wistar rats were actively or passively sensitized. Active sensitization was performed by injection of both dinitrophenylated-ovalbumin (DNP-OA) and Bordetella pertussis. Nine days later, DNP-OA was injected into the right hind footpad. This antigen challenge induced a biphasic footpad swelling that consisted of an early-phase (EPR) and a late-phase response (LPR). In rats passively sensitized with rat anti-DNP-OA serum, DNP-OA induced only EPR. The EPR was suppressed by disodium cromoglycate, a mast cell stabilizer, but not by cyclosporin A, an immunosuppressant, while the LPR was suppressed by cyclosporin A. Furthermore, to investigate these two allergic responses determined by the interactions between the hapten and the carrier proteins, two distinct haptenated antigens were created. DNP-Ascaris (DNP-As) induced a marked EPR and LPR in DNP-As-sensitized rats. However, DNP-As induced only EPR in DNP-OA-sensitized rats, indicating that the usage of the same carrier protein in both sensitization and challenge was necessary for induction of LPR. These data suggest that this actively sensitization model in which EPR and LPR are functionally distinguishable should be useful for evaluating the efficacy of antiallergic compounds.
我们建立了一种新的简便模型来研究过敏机制并评估抗过敏化合物的效果。雄性Wistar大鼠被主动或被动致敏。主动致敏通过注射二硝基苯基化卵清蛋白(DNP - OA)和百日咳博德特氏菌来进行。九天后,将DNP - OA注射到右后足垫。这种抗原激发诱导了一种双相足垫肿胀,其由早期反应(EPR)和晚期反应(LPR)组成。在用大鼠抗DNP - OA血清被动致敏的大鼠中,DNP - OA仅诱导EPR。EPR被肥大细胞稳定剂色甘酸钠抑制,但不被免疫抑制剂环孢素A抑制,而LPR被环孢素A抑制。此外,为了研究由半抗原与载体蛋白之间的相互作用所决定的这两种过敏反应,制备了两种不同的半抗原化抗原。DNP - 蛔虫(DNP - As)在DNP - As致敏的大鼠中诱导出明显的EPR和LPR。然而,DNP - As在DNP - OA致敏的大鼠中仅诱导EPR,这表明在致敏和激发过程中使用相同的载体蛋白对于诱导LPR是必要的。这些数据表明,这种EPR和LPR在功能上可区分的主动致敏模型对于评估抗过敏化合物的疗效应该是有用的。