Mast cells in citric acid-induced airway constriction and cough

Inhalation of citric acid (CA) causes airway constriction and coughing. To investigate the role of mast cells in CA-induced airway constriction and cough, three experiments using guinea pigs were carried out. In the first experiment, we used compound 48/80 to deplete mast cells, cromolyn sodium to stabilize mast cells, MK-886 to inhibit synthesis of leukotrienes, pyrilamine to antagonize histamine H1 receptor, methysergide to antagonize serotonin receptor, and indomethacin to inhibit cyclooxygenase. In the second experiment, compound 48/80-pretreated animals were divided into 2 parts; the first one was used to test the role of exogenous leukotriene (LT) C4, while the second one to test the role of exogenous histamine. Decreases in respiratory compliance (Crs) and forced expiratory volume in 0.1 sec (FEV0.1) were used as indicators for airway constriction in anesthetized guinea pigs. CA-induced cough was recorded for 12 min using a barometric body plethysmograph in conscious animals. In the third experiment, the activation of mast cells upon CA inhalation was investigated by determining lung tissue or arterial plasma histamine concentration in animals. Exposure to CA induced marked airway constriction and increase in cough number. Compound 48/80, cromolyn sodium, MK-886 and pyrilamine, but not indomethacin or methysergide, significantly attenuated CA-induced airway constriction and cough. Injection of LTC4 or histamine caused a significant increase in CA-induced airway constriction and cough in compound 48/80-pretreated animals. In addition, CA inhalation caused significant increase in lung tissue and plasma histamine concentrations, which were blocked by compound 48/80 pretreatment. These results suggest that mast cells play an important role in CA aerosol inhalation-induced airway constriction and cough via perhaps mediators including LTs and histamine.

吸入柠檬酸（CA）可诱发气道收缩与咳嗽。为探究肥大细胞在CA诱导的气道收缩及咳嗽中的作用，本研究以豚鼠为模型开展了三项实验。实验一采用化合物48/80耗竭肥大细胞、色甘酸钠稳定肥大细胞、MK-886抑制白三烯合成、吡拉明拮抗组胺H1受体、美西麦角拮抗5-羟色胺受体，以及吲哚美辛抑制环氧合酶。实验二将经化合物48/80预处理的豚鼠分为两组：一组用于检测外源性白三烯（LT）C4的作用，另一组用于检测外源性组胺的作用。以麻醉豚鼠的呼吸顺应性（Crs）与0.1秒用力呼气容积（FEV0.1）的下降作为气道收缩的评价指标；对清醒豚鼠采用体积描记箱记录12分钟内的CA诱导性咳嗽。实验三通过检测动物肺组织及动脉血浆中的组胺浓度，探究CA吸入后肥大细胞的活化状态。研究结果显示：CA暴露可引发显著的气道收缩与咳嗽次数增多；化合物48/80、色甘酸钠、MK-886及吡拉明可显著缓解CA诱导的气道收缩与咳嗽，而吲哚美辛与美西麦角无明显干预效果；向经化合物48/80预处理的豚鼠注射LTC4或组胺，可显著增强CA诱导的气道收缩与咳嗽。此外，CA吸入可显著升高肺组织及血浆组胺浓度，该效应可被化合物48/80预处理阻断。综上，肥大细胞在柠檬酸气溶胶吸入诱导的气道收缩与咳嗽中发挥重要作用，其机制可能涉及白三烯与组胺等炎性介质。