Solèr M, Sielczak M W, Abraham W M
Division of Pulmonary Disease, Mount Sinai Medical Center, Miami Beach, Florida 33140.
J Appl Physiol (1985). 1989 Jul;67(1):406-13. doi: 10.1152/jappl.1989.67.1.406.
We studied the effects of WEB-2086, a specific antagonist of platelet-activating factor (PAF), on the development of antigen-induced airway hyperresponsiveness and inflammation in sheep (n = 8). For these studies, airway responsiveness was determined from slopes of carbachol dose-response curves (DRC) performed at base line (prechallenge) and 2 h after Ascaris suum antigen challenges in the following three protocols: 1) antigen challenge alone (control trial), 2) WEB-2086 (1 mg/kg iv) given 30 min before antigen challenge (WEB pretreatment), and 3) WEB-2086 given 2 h after antigen challenge, immediately before the postchallenge DRC (WEB posttreatment). Airway inflammation was assessed by bronchoalveolar lavage (BAL) before antigen challenge and after the postchallenge DRC for each trial. A. suum challenge resulted in acute increases in specific lung resistance that were not different among the three trials. Antigen challenge (control trial) caused a 93% increase (P less than 0.05) in the slope of the carbachol DRC when compared with the prechallenge value. WEB pretreatment (1 mg/kg) reduced (P less than 0.05) this antigen-induced hyperresponsiveness, whereas pretreatment with a 3-mg/kg dose completely prevented it. WEB posttreatment was ineffective in blocking this hyperresponsiveness. BAL neutrophils increased after antigen challenge in the control trial and when WEB-2086 was given after antigen challenge (P less than 0.05). Pretreatment with WEB-2086 (1 or 3 mg/kg) prevented this neutrophilia. This study provides indirect evidence for antigen-induced PAF release in vivo and for a role of endogenous PAF in the modulation of airway responsiveness and airway inflammation after antigen-induced bronchoconstriction in sheep.
我们研究了血小板活化因子（PAF）的特异性拮抗剂WEB-2086对绵羊（n = 8）抗原诱导的气道高反应性和炎症发展的影响。在以下三个方案中，通过基线（激发前）和猪蛔虫抗原激发后2小时的卡巴胆碱剂量反应曲线（DRC）斜率来确定气道反应性：1）单独抗原激发（对照试验），2）在抗原激发前30分钟静脉注射WEB-2086（1 mg/kg）（WEB预处理），3）在抗原激发后2小时，即激发后DRC之前立即给予WEB-2086（WEB后处理）。通过每次试验抗原激发前和激发后DRC后的支气管肺泡灌洗（BAL）评估气道炎症。猪蛔虫激发导致特异性肺阻力急性增加，这在三个试验中没有差异。与激发前值相比，抗原激发（对照试验）使卡巴胆碱DRC斜率增加了93%（P < 0.05）。WEB预处理（1 mg/kg）降低了（P < 0.05）这种抗原诱导的高反应性，而3 mg/kg剂量的预处理则完全阻止了它。WEB后处理在阻断这种高反应性方面无效。在对照试验中以及在抗原激发后给予WEB-2086时，BAL中性粒细胞在抗原激发后增加（P < 0.05）。用WEB-2086（1或3 mg/kg）预处理可防止这种中性粒细胞增多。这项研究为体内抗原诱导的PAF释放以及内源性PAF在绵羊抗原诱导的支气管收缩后调节气道反应性和气道炎症中的作用提供了间接证据。
