Toxocara canis-induced airway eosinophilia and tracheal hyporeactivity in guinea pigs and mice.
Guinea pigs and mice infected with the parasitic worms Toxocara canis developed airway inflammation and tracheal hyporesponsiveness. Preceding inflammatory cell infiltration a brief hyperreactive response occurred in guinea pigs to histaminergic receptor stimulation at 3 days post infection (p.i.) and in mice to acetylcholine receptor stimulation at 1 day p.i. Few but large eosinophilic inflammatory foci developed in guinea pigs at 14 days p.i. Mice demonstrated progressive multifocal inflammation from 7 days p.i. In addition to eosinophils mouse airways were infiltrated by lymphocytes, forming perivascular and (partial) peribronchial infiltrates in an oedematous submucosa. The inflammation persisted in mice for > or = 3 months and likewise persisted tracheal hyporeactivity. Incubation of tracheae of non-infected mice with pulmonary inflammatory cells caused a significant decrease in cholinergic receptor responsiveness. This downward shift was prevented by 60% when a cyclooxygenase inhibitor was added to the incubation medium but not when inhibitors of lipoxygenase and superoxide formation were added, suggesting the involvement of prostaglandin E2. This suggestion was supported by the finding of significantly increased prostaglandin E2 concentrations in the bronchoalveolar lavage fluid at 14 and 28 days p.i. It was concluded that tracheal hyporeactivity coincided with the presence of large numbers of eosinophils in the airways of both, guinea pigs and mice and that prostaglandin E2 involvement was conceivable.
Buijs
J
J
Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, The Netherlands.
Egbers
M W
MW
Nijkamp
F P
FP
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002217:Carbachol / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004802:Eosinophilia / Q000469:parasitology* / Q000473:pathology / Q000503:physiopathology; D004804:Eosinophils / Q000473:pathology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008137:Longitudinal Studies; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018721:Muscarinic Agonists / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011657:Pulmonary Eosinophilia / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology; D011950:Receptors, Cholinergic / Q000378:metabolism; D011968:Receptors, Histamine / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D017166:Toxocara canis; D014120:Toxocariasis / Q000150:complications*; D014132:Trachea / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D014133:Tracheal Diseases / Q000469:parasitology* / Q000473:pathology / Q000503:physiopathology
D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D011950:Receptors, Cholinergic; D011968:Receptors, Histamine; D006632:Histamine; D002217:Carbachol; D015232:Dinoprostone