Lewis C A, Johnson A, Broadley K J
Department of Pharmacology, Welsh School of Pharmacy, University of Wales, Cardiff, UK.
Int J Immunopharmacol. 1996 Jun-Jul;18(6-7):415-22. doi: 10.1016/s0192-0561(96)00055-0.
Guinea-pigs were sensitized by i.p. injection of 10 micrograms OA and 100 mg aluminium hydroxide in 1 ml normal saline. Fourteen to twenty-one days after sensitization, animals were exposed to macroshock (1% OA for 2 min) or microshock (0.01% for 60 min) inhalation challenges with OA. Animals were protected against fatal anaphylaxis in the case of macroshocks with mepyramine (30mg/kg i.p.) 30 min before exposure. Specific airway conductance (sGaw) was measured in conscious animals by whole body plethysmography at intervals up to 72 h after challenge. An early phase bronchoconstriction peaked significantly (P < 0.05) at 15 min after both macroshock and microshock OA exposures, with maximum falls in sGaw of 70.8 +/- 3.8 and -40.0 +/- 5.9%, respectively. These had resolved after 5 h. A late phase bronchoconstriction peaked variably between 17 and 24 h: the mean peak falls in sGaw after the macro- and microshock challenges were significantly different from baseline (P < 0.05), at -21.6 +/- 3.7 and -38.0 +/- 3.9%, respectively. Control exposures of OA-sensitized guinea-pigs to saline for either 2 or 60 min, in place of OA, produced no significant variation in sGaw values over the predicted early and late phases. Bronchoalveolar lavage (BAL) performed at 5 or 24 h after OA challenge revealed significant increases in total cell numbers (P < 0.05) at 5 and 24 h after the OA macroshock challenge and at 24 h after the microshock, compared with saline challenges. Differential cell counts showed a significant (P < 0.05) increase in the proportion of neutrophils at 5 h and of neutrophils and eosinophils at 24 h after the macroshock exposure to OA, compared with saline controls. A significant (P < 0.05) increase in the proportion of eosinophils also occurred in BAL fluid at 24 h after microshock OA challenge. Neutrophils, however, did not alter at 24 h, yet a late phase bronchoconstriction was recorded. Thus, macroshock (with mepyramine cover) and microshock (without mepyramine cover) OA challenges result in both early and late phase bronchoconstrictions. The late phase is associated with influx of eosinophils in both models but neutrophils only appear after the macroshock, indicating that late phase responses may not involve neutrophil infiltration to the airways.
通过腹腔注射10微克卵清蛋白（OA）和100毫克氢氧化铝于1毫升生理盐水中使豚鼠致敏。致敏后14至21天，动物接受卵清蛋白的大剂量激发（1%卵清蛋白，持续2分钟）或小剂量激发（0.01%，持续60分钟）吸入试验。在暴露前30分钟，用吡苄明（30毫克/千克腹腔注射）保护动物免受大剂量激发所致的致命性过敏反应。在激发后长达72小时的时间间隔内，通过全身体积描记法在清醒动物中测量比气道传导率（sGaw）。大剂量和小剂量卵清蛋白激发后，早期支气管收缩在15分钟时均显著达到峰值（P < 0.05），sGaw的最大下降分别为70.8 +/- 3.8%和 -40.0 +/- 5.9%。这些在5小时后消退。晚期支气管收缩在17至24小时之间达到不同程度的峰值：大剂量和小剂量激发后sGaw的平均峰值下降与基线相比有显著差异（P < 0.05），分别为 -21.6 +/- 3.7%和 -38.0 +/- 3.9%。用生理盐水代替卵清蛋白对卵清蛋白致敏的豚鼠进行2分钟或60分钟的对照暴露，在预测的早期和晚期，sGaw值没有显著变化。在卵清蛋白激发后5小时或24小时进行支气管肺泡灌洗（BAL），与生理盐水激发相比，在卵清蛋白大剂量激发后5小时和24小时以及小剂量激发后24小时，总细胞数显著增加（P < 0.05）。差异细胞计数显示，与生理盐水对照相比，在大剂量卵清蛋白激发后5小时，中性粒细胞比例显著增加（P < 0.05），在24小时，中性粒细胞和嗜酸性粒细胞比例显著增加。在小剂量卵清蛋白激发后24小时，支气管肺泡灌洗液中嗜酸性粒细胞比例也显著增加（P < 0.05）。然而，在24小时时中性粒细胞没有变化，但记录到了晚期支气管收缩。因此，大剂量激发（用吡苄明保护）和小剂量激发（不用吡苄明保护）卵清蛋白均导致早期和晚期支气管收缩。在两种模型中，晚期均与嗜酸性粒细胞的流入有关，但中性粒细胞仅在大剂量激发后出现，这表明晚期反应可能不涉及中性粒细胞向气道的浸润。
