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血小板活化因子拮抗剂BN 52021对豚鼠不同形式主动过敏反应的干扰:加强注射的重要性

Interference of BN 52021, an antagonist of PAF, with different forms of active anaphylaxis in the guinea-pig: importance of the booster injection.

作者信息

Desquand S, Lefort J, Dumarey C, Vargaftig B B

机构信息

Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur- Institut National de la Santé et de la Recherche Médicale, Paris, France.

出版信息

Br J Pharmacol. 1991 Mar;102(3):687-95. doi: 10.1111/j.1476-5381.1991.tb12234.x.

DOI:10.1111/j.1476-5381.1991.tb12234.x
PMID:1285397
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1917931/
Abstract
  1. BN 52021, an antagonist of platelet activating factor (PAF), was inactive against bronchoconstriction in guinea-pigs sensitized with low amounts of ovalbumin (OA) injected twice, at a 14 day interval and challenged i.v. 7 days later. 2. Serum IgG titers increased for 7 weeks after the booster injection at day 14 and returned to low levels at day 96. 3. Administered by the intratracheal (i.t.) route at 1 mg, BN 52021 failed to inhibit bronchoconstriction induced by the i.t. administration of OA to guinea-pigs tested 7, 28, 56 and 84 days after the booster injection, even when the titers of circulating IgG had declined with time. BN 52021 was also inactive against bronchoconstriction in guinea-pigs boosted at day 98 and tested 7 days later and against contractions and thromboxane (Tx) B2 and histamine release induced by OA-challenged parenchymal lung strips from the boosted guinea-pigs. 4. Sensitized unboosted guinea-pigs displayed reduced IgG serum titers. Used 21 or 70 days after the sensitizing injection, they did develop bronchoconstriction upon the i.t. instillation of OA, which was blocked by BN 52021. The latter also inhibited OA-induced contractions of lung parenchymal strips from these unboosted guinea-pigs. 5. When boosted and non-boosted guinea-pigs received OA i.t. and bronchoalveolar lavage fluid was collected 10 min later, the number of eosinophils increased markedly in boosted, but not in non-boosted guinea-pigs. 6. The booster injection of antigen thus modifies the response of the lung and PAF appears to be relevant for antigen-induced bronchoconstriction in unboosted animals, but loses its major role following the booster injection.
摘要
  1. BN 52021是一种血小板活化因子(PAF)拮抗剂,对间隔14天两次注射少量卵清蛋白(OA)致敏、7天后静脉注射激发的豚鼠支气管收缩无活性。2. 加强注射后第14天,血清IgG滴度升高7周,并在第96天恢复到低水平。3. 以1毫克的剂量经气管内(i.t.)途径给药,BN 52021未能抑制在加强注射后7、28、56和84天测试的豚鼠经气管内给予OA所诱导的支气管收缩,即使循环IgG滴度随时间下降。BN 52021对在第98天加强免疫并在7天后测试的豚鼠的支气管收缩也无活性,并且对来自加强免疫豚鼠的OA激发的肺实质条带的收缩、血栓素(Tx)B2和组胺释放也无活性。4. 未加强免疫的致敏豚鼠血清IgG滴度降低。在致敏注射后21天或70天使用时,它们在经气管内滴注OA后确实出现支气管收缩,这被BN 52021阻断。后者也抑制了这些未加强免疫豚鼠的肺实质条带的OA诱导的收缩。5. 当加强免疫和未加强免疫的豚鼠经气管内给予OA并在10分钟后收集支气管肺泡灌洗液时,加强免疫的豚鼠中嗜酸性粒细胞数量显著增加,而未加强免疫的豚鼠中则没有。6. 因此,抗原的加强注射改变了肺的反应,PAF似乎与未加强免疫动物中抗原诱导的支气管收缩有关,但在加强注射后失去了其主要作用。

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本文引用的文献

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Antigen-induced bronchial anaphylaxis in actively sensitized guinea-pigs. Pattern of response in relation to immunization regimen.主动致敏豚鼠中抗原诱导的支气管过敏反应。与免疫方案相关的反应模式。
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Pharmacological control of the in vivo passive anaphylactic shock by the PAF-acether antagonist compound BN 52021.
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A study with BN 52021 demonstrates the involvement of PAF-acether in IgE-dependent anaphylactic bronchoconstriction.一项关于BN 52021的研究表明血小板活化因子(PAF-乙酰醚)参与了IgE依赖性过敏性支气管收缩。
Prostaglandins. 1986 Jul;32(1):121-6. doi: 10.1016/0090-6980(86)90153-x.
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Inhibition of antigen-induced lung anaphylaxis in the guinea-pig by BN 52021 a new specific paf-acether receptor antagonist isolated from Ginkgo biloba.
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Eur J Pharmacol. 1987 Aug 21;140(3):311-21. doi: 10.1016/0014-2999(87)90288-3.