Buckley T L, Nijkamp F P
Department of Pharmacology, Faculty of Pharmacy, Utrecht University, The Netherlands.
Am J Respir Crit Care Med. 1994 Feb;149(2 Pt 1):400-7. doi: 10.1164/ajrccm.149.2.8306037.
The aim of this study was to investigate the possible role of capsaicin-sensitive nerves in a pulmonary delayed-type hypersensitivity (DTH) reaction. Mice (Balb/c) were skin-sensitized with dinitrofluorobenzene (DNFB; 0.5%, 100 microliters) on two consecutive days and challenged intranasally 5 days later with dinitrobenzene sulphonic acid (0.6%, 50 microliters). Sensitized mice exhibited tracheal hyperreactivity to carbachol 24 and 48 h after challenge; however, no hyperreactivity was observed 2 h after challenge. At 24 h, but not at 48 h, hyperreactivity was associated with antigen-specific lymphocyte accumulation in bronchoalveolar lavage fluid (BALF). Capsaicin pretreatment, resulting in the depletion of sensory neuropeptides, virtually abolished hyperreactivity to carbachol 24 and 48 h after challenge in sensitized mice. Although at 24 h after challenge the lymphocyte population was elevated in the BALF collected from capsaicin-pretreated mice, this accumulation was not antigen-specific. Additionally, there was an increase in polymorphonuclear leukocyte accumulation (neutrophils and eosinophils) in the BALF collected from capsaicin-pretreated mice at this time point, but this increase was more profound in the sensitized group. In summary, tracheal hyperreactivity and cellular accumulation are prominent features of the lymphocyte-associated DTH reaction induced by DNFB in the mouse lung. Evidence presented in this report highlights the possible importance of sensory neuropeptides in pulmonary inflammation and airways hyperreactivity.
本研究的目的是探讨辣椒素敏感神经在肺部迟发型超敏反应(DTH)中的可能作用。连续两天用二硝基氟苯(DNFB;0.5%,100微升)对小鼠(Balb/c)进行皮肤致敏,5天后用二硝基苯磺酸(0.6%,50微升)进行鼻内激发。致敏小鼠在激发后24小时和48小时对卡巴胆碱表现出气管高反应性;然而,在激发后2小时未观察到高反应性。在24小时而非48小时,高反应性与支气管肺泡灌洗液(BALF)中抗原特异性淋巴细胞积聚有关。辣椒素预处理导致感觉神经肽耗竭,实际上消除了致敏小鼠在激发后24小时和48小时对卡巴胆碱的高反应性。尽管在激发后24小时,从辣椒素预处理小鼠收集的BALF中淋巴细胞数量增加,但这种积聚不是抗原特异性的。此外,在这个时间点,从辣椒素预处理小鼠收集的BALF中多形核白细胞(中性粒细胞和嗜酸性粒细胞)积聚增加,但在致敏组中这种增加更为明显。总之,气管高反应性和细胞积聚是DNFB诱导的小鼠肺部淋巴细胞相关DTH反应的突出特征。本报告提供的证据突出了感觉神经肽在肺部炎症和气道高反应性中的可能重要性。