Mucosal exudation associated with a pulmonary delayed-type hypersensitivity reaction in the mouse. Role for the tachykinins.
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.
Buckley
T L
TL
Department of Pharmacology, Utrecht University, The Netherlands.
Nijkamp
F P
FP
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004487:Edema / Q000276:immunology; D005122:Exudates and Transudates / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008168:Lung / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D015320:Tachykinins / Q000037:antagonists & inhibitors / Q000502:physiology*
D007211:Indoles; D054833:Isoindoles; D010446:Peptide Fragments; D015320:Tachykinins; C058636:calcitonin gene-related peptide (8-37); C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin