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血小板活化因子气雾剂暴露诱导豚鼠肺气道嗜酸性粒细胞积聚:抗哮喘药物的作用

Eosinophil accumulation in pulmonary airways of guinea-pigs induced by exposure to an aerosol of platelet-activating factor: effect of anti-asthma drugs.

作者信息

Sanjar S, Aoki S, Boubekeur K, Chapman I D, Smith D, Kings M A, Morley J

机构信息

Preclinical Research, Sandoz Ltd, Basel, Switzerland.

出版信息

Br J Pharmacol. 1990 Feb;99(2):267-72. doi: 10.1111/j.1476-5381.1990.tb14692.x.

Abstract
  1. Exposure of guinea-pigs to aerosols of platelet activating factor (PAF) (0.01 to 100 micrograms ml-1) induced a dose-dependent increased incidence of eosinophils in bronchoalveolar lavage fluid (BAL) at 48 h. Total leucocyte numbers and the percentages of lymphocytes and neutrophils were unchanged in BAL fluid. 2. Increased numbers of eosinophils were detected in BAL 1 h after exposure to PAF but eosinophilia was not maximal until 48 h. One week after exposure to PAF, the percentage of eosinophils in BAL was within the normal range. 3. Depletion of circulating platelets or neutrophils by intravenous injection of specific antisera did not modify accumulation of eosinophils in the airway lumen following inhalation of PAF (10 micrograms ml-1). 4. PAF-induced pulmonary airway eosinophil accumulation was inhibited by treatment with SDZ 64-412, a selective PAF-antagonist, whether the compound was administered before, or 30 min after, inhalation of PAF. 5. Pulmonary airway eosinophil accumulation due to inhaled PAF (10 micrograms ml-1) was inhibited by prior treatment with aminophylline, cromoglycate, ketotifen, dexamethasone and AH 21-132. 6. Pulmonary airway eosinophil accumulation due to inhaled PAF (10 micrograms ml-1) was not inhibited by prior treatment with indomethacin, salbutamol or mepyramine.
摘要
  1. 将豚鼠暴露于血小板活化因子(PAF)气雾剂(0.01至100微克/毫升)中48小时后,支气管肺泡灌洗液(BAL)中嗜酸性粒细胞的发生率呈剂量依赖性增加。BAL液中的白细胞总数以及淋巴细胞和中性粒细胞的百分比未发生变化。2. 在暴露于PAF后1小时,BAL中检测到嗜酸性粒细胞数量增加,但嗜酸性粒细胞增多直到48小时才达到最大值。暴露于PAF一周后,BAL中嗜酸性粒细胞的百分比在正常范围内。3. 通过静脉注射特异性抗血清耗尽循环血小板或中性粒细胞,并不会改变吸入PAF(10微克/毫升)后气道腔内嗜酸性粒细胞的积聚。4. 用选择性PAF拮抗剂SDZ 64-412治疗可抑制PAF诱导的肺气道嗜酸性粒细胞积聚,无论该化合物是在吸入PAF之前还是之后30分钟给药。5. 预先用氨茶碱、色甘酸、酮替芬、地塞米松和AH 21-132治疗,可抑制吸入PAF(10微克/毫升)引起的肺气道嗜酸性粒细胞积聚。6. 预先用吲哚美辛、沙丁胺醇或美吡拉敏治疗,不会抑制吸入PAF(10微克/毫升)引起的肺气道嗜酸性粒细胞积聚。

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