title: Airways hyperreactivity and cellular accumulation in a delayed-type hypersensitivity reaction in the mouse. Modulation by capsaicin-sensitive nerves.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Utrecht University, The Netherlands.
authors.forename: T L
authors.initials: TL
authors.lastname: Buckley
authors.forename: F P
authors.initials: FP
authors.lastname: Nijkamp
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D006968:Hypersensitivity, Delayed / Q000503:physiopathology*; D007114:Immunization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009411:Nerve Endings / Q000187:drug effects; D011292:Premedication; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D012882:Skin Tests; D015320:Tachykinins / Q000502:physiology; D014132:Trachea / Q000294:innervation* / Q000503:physiopathology
chemical_list: D015320:Tachykinins; D002217:Carbachol; D004139:Dinitrofluorobenzene; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin