Buckley T L, Nijkamp F P
Department of Pharmacology, Utrecht University, The Netherlands.
J Immunol. 1994 Nov 1;153(9):4169-78.
In this study, the role for sensory neuropeptides in the induction of pulmonary inflammation associated with a delayed-type hypersensitivity (DTH) reaction in the mouse lung was investigated. Dinitrofluorobenzene (DNFB) was used as the sensitizing hapten and dinitrobenzene sulfonic acid was used as the intranasal challenge. Two hours after the challenge, no hapten-specific differences were observed between vehicle- and DNFB-sensitized mice. However, mucosal exudation and leukocyte accumulation (mononuclear leukocytes and neutrophils) were enhanced in the DNFB group 24 h after the challenge. In additional experiments we investigated whether the sensory nerves and specific sensory neuropeptides play a role in this pulmonary DTH reaction. The selective NK1 antagonist (RP 67580; 5.10(-9) mol/mouse), administered 5 min before and 1 h after the challenge, suppressed mucosal exudation and leukocyte accumulation in the airways 24 h after the challenge. In contrast, the selective calcitonin gene-related peptide (CGRP) antagonist, CGRP8-37 (5.10(-9) mol/mouse) had no effect on the pulmonary DTH reaction. Surprisingly, the depletion of all sensory neuropeptides resulted in an enhancement of mucosal exudation in vehicle- and DNFB-sensitized mice 24 h after the challenge. In conclusion, these results demonstrate that the tachykinins are important in mediating mucosal exudation and leukocyte accumulation associated with the DTH reaction in mouse airways. However, the findings in neuropeptide-depleted mice suggest that the sensory nerves may also play a protective role in mouse airways.
在本研究中，我们调查了感觉神经肽在小鼠肺部迟发型超敏反应（DTH）相关的肺部炎症诱导中的作用。使用二硝基氟苯（DNFB）作为致敏半抗原，二硝基苯磺酸作为鼻内激发剂。激发后两小时，在赋形剂致敏和DNFB致敏的小鼠之间未观察到半抗原特异性差异。然而，在激发后24小时，DNFB组的粘膜渗出和白细胞积聚（单核白细胞和中性粒细胞）增强。在额外的实验中，我们研究了感觉神经和特定的感觉神经肽是否在这种肺部DTH反应中起作用。在激发前5分钟和激发后1小时给予选择性NK1拮抗剂（RP 67580；5×10⁻⁹mol/小鼠），可抑制激发后24小时气道中的粘膜渗出和白细胞积聚。相反，选择性降钙素基因相关肽（CGRP）拮抗剂CGRP8 - 37（5×10⁻⁹mol/小鼠）对肺部DTH反应没有影响。令人惊讶的是，所有感觉神经肽的耗竭导致在激发后24小时赋形剂致敏和DNFB致敏的小鼠中粘膜渗出增强。总之，这些结果表明速激肽在介导与小鼠气道DTH反应相关的粘膜渗出和白细胞积聚中很重要。然而，神经肽耗竭小鼠的研究结果表明感觉神经在小鼠气道中也可能起保护作用。
