T cell-mediated induction of airway hyperresponsiveness and altered lung functions in mice are independent of increased vascular permeability and mononuclear cell infiltration.
Previously it was demonstrated that during delayed-type hypersensitivity reactions (DTH) to picryl chloride (PCl) in murine lungs, as a model for cellular IgE-independent immunity, tracheal hyperreactivity and increased pulmonary resistance are induced. In the present study it is demonstrated that after pretreatment with 5HT-2 antagonists, such as ketanserin and methysergide, DTH lung reactions to PCl in mice are suppressed. The increase in vascular permeability, detectable at 2 h after intranasal hapten challenge and probably necessary for the development of a classic DTH reaction, as was demonstrated in skin DTH models, as well as the classic late inflammatory component of lung DTH, is inhibited. However, in vitro tracheal hyperreactivity to the cholinergic receptor agonist carbachol and increased pulmonary resistance in vivo, both induced during the development of these inflammatory DTH lung reactions, are not affected by 5HT-2 receptor antagonist pretreatment. These results indicate that the actual presence of increased vascular permeability and mononuclear infiltrates is not a prerequisite for the development of changed lung functions and tracheal hyperresponsiveness. Thus in mice, serotonin-independent mechanisms that appear during T cell-dependent lung immune reactions induce airway hyperresponsiveness and increased pulmonary resistance.
Garssen
J
J
Department of Pharmacology, Faculty of Pharmacy, Utrecht University, The Netherlands.
Van Loveren
H
H
Van Der Vliet
H
H
Bot
H
H
Nijkamp
F P
FP
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000503:physiopathology*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000503:physiopathology; D007114:Immunization; D016219:Immunotherapy, Adoptive / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology*; D008168:Lung / Q000187:drug effects / Q000503:physiopathology*; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D012702:Serotonin Antagonists / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000503:physiopathology
D012702:Serotonin Antagonists