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选择性血小板活化因子拮抗剂BN 52021对血小板活化因子和抗原诱导的支气管高反应性及嗜酸性粒细胞聚集的影响。

The effect of the selective PAF antagonist BN 52021 on PAF- and antigen-induced bronchial hyper-reactivity and eosinophil accumulation.

作者信息

Coyle A J, Urwin S C, Page C P, Touvay C, Villain B, Braquet P

机构信息

Department of Pharmacology, King's College, London University, England.

出版信息

Eur J Pharmacol. 1988 Mar 22;148(1):51-8. doi: 10.1016/0014-2999(88)90453-0.

Abstract

Sensitised guinea-pigs were exposed to an aerosol of ovalbumin (100-500 micrograms/ml) and normal animals were exposed to an aerosol of platelet activating factor (PAF) (250-1000 micrograms/ml). Twenty-four hours later, bronchial reactivity was assessed by measurement of air overflow in response to i.v. histamine or acetylcholine using the Konsett-Rossler technique. Additionally, bronchoalveolar lavage was performed by washing the lungs with 10 ml of 0.9% saline and differential counts obtained to assess the ability of PAF and antigen to elicit pulmonary inflammatory cell recruitment. Both PAF and antigen exposure produced a dose-related increase in bronchial reactivity, while treatment with the vehicle (either 0.25% bovine serum albumin or 0.9% saline) had no effect on airway responsiveness. Furthermore, both PAF and antigen exposure produced a selective accumulation of eosinophils into the airways. There was no significant change in the number of neutrophils, macrophages or lymphocytes. The selective PAF antagonist BN52021 inhibited both the development of bronchial hyper-reactivity and the eosinophil influx into the airways induced by PAF or antigen exposure. These observations suggest that PAF has a central role to play in the antigen induced eosinophil accumulation and subsequent bronchial hyper-reactivity.

摘要

将致敏豚鼠暴露于卵清蛋白气雾剂(100 - 500微克/毫升)中,正常动物暴露于血小板活化因子(PAF)气雾剂(250 - 1000微克/毫升)中。24小时后,采用Konsett - Rossler技术,通过测量静脉注射组胺或乙酰胆碱后的空气溢出量来评估支气管反应性。此外,用10毫升0.9%生理盐水冲洗肺部进行支气管肺泡灌洗,并进行细胞分类计数,以评估PAF和抗原引发肺炎症细胞募集的能力。PAF和抗原暴露均导致支气管反应性呈剂量依赖性增加,而用赋形剂(0.25%牛血清白蛋白或0.9%生理盐水)处理对气道反应性无影响。此外,PAF和抗原暴露均导致嗜酸性粒细胞选择性积聚到气道中。中性粒细胞、巨噬细胞或淋巴细胞数量无显著变化。选择性PAF拮抗剂BN52021抑制了PAF或抗原暴露诱导的支气管高反应性的发展以及嗜酸性粒细胞流入气道。这些观察结果表明,PAF在抗原诱导的嗜酸性粒细胞积聚和随后的支气管高反应性中起核心作用。

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