Nobata Kouichi, Kurashima Kazuyoshi, Fujimura Masaki, Abo Miki, Ishiura Yoshihisa, Kasahara Kazuo, Nakao Shinji
Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
Eur J Pharmacol. 2005 Sep 27;520(1-3):150-5. doi: 10.1016/j.ejphar.2005.07.032.
Lysophosphatidylcholine is increased in the airway of bronchial asthma, but its role is not clear. We investigated the role of lysophosphatidylcholine in asthma in anaesthetized, mechanically ventilated guinea pigs. Pressure at the airway opening was measured as an index of bronchial response. Increasing doses of lysophosphatidylcholine (1--10 mg/ml) were inhaled and then bronchoalveolar lavage was carried out. 100 and 200 microg/ml methacholine were inhaled 10 min after inhalation of 2.5 mg/ml lysophosphatidylcholine, 10 mg/ml dipalmitoyl phosphatidylcholine and 10 mg/ml glycerophosphocholine, all of which per se did not change the pressure at the airway opening. Effect of 1.0 microg/kg salbutamol, or 60 mg/kg diphenhydramine on the lysophosphatidylcholine-induced increase in the pressure at the airway opening was investigated. Inhalation of lysophosphatidylcholine dose-dependently increased the pressure at the airway opening and increased bronchial responsiveness to methacholine. On the other hand, inhalation of dipalmitoyl phosphatidylcholine decreased the pressure at the airway opening and decreased bronchial responsiveness to methacholine. Intravenously administered salbutamol, but not diphenhydramine, prevented the lysophosphatidylcholine-induced increase in the pressure at the airway opening. The percentage of leukocytes in bronchoalveolar lavage fluid did not change significantly at least within 20 min after the lysophosphatidylcholine inhalation. Lysophosphatidylcholine causes bronchoconstriction and enhances bronchial responsiveness without inducing leukocyte infiltration in the airway, suggesting that lysophosphatidylcholine may be a new bronchoconstrictor mediator in bronchial asthma.
溶血磷脂酰胆碱在支气管哮喘患者气道中含量升高，但其作用尚不清楚。我们在麻醉、机械通气的豚鼠中研究了溶血磷脂酰胆碱在哮喘中的作用。测量气道开口处的压力作为支气管反应的指标。吸入递增剂量的溶血磷脂酰胆碱（1-10mg/ml），然后进行支气管肺泡灌洗。在吸入2.5mg/ml溶血磷脂酰胆碱、10mg/ml二棕榈酰磷脂酰胆碱和10mg/ml甘油磷酸胆碱10分钟后，吸入100和200μg/ml乙酰甲胆碱，所有这些本身均未改变气道开口处的压力。研究了1.0μg/kg沙丁胺醇或60mg/kg苯海拉明对溶血磷脂酰胆碱诱导的气道开口处压力升高的影响。吸入溶血磷脂酰胆碱可剂量依赖性地增加气道开口处的压力，并增加支气管对乙酰甲胆碱的反应性。另一方面，吸入二棕榈酰磷脂酰胆碱可降低气道开口处的压力，并降低支气管对乙酰甲胆碱的反应性。静脉注射沙丁胺醇而非苯海拉明可预防溶血磷脂酰胆碱诱导的气道开口处压力升高。溶血磷脂酰胆碱吸入后至少20分钟内，支气管肺泡灌洗液中白细胞的百分比没有明显变化。溶血磷脂酰胆碱可引起支气管收缩并增强支气管反应性，而不会诱导气道中的白细胞浸润，这表明溶血磷脂酰胆碱可能是支气管哮喘中的一种新的支气管收缩介质。
