title: Eosinophil recruitment into guinea pig lungs after PAF-acether and allergen administration. Modulation by prostacyclin, platelet depletion, and selective antagonists.
abstract: Intravenous administration of PAF-acether to the guinea pig induces bronchoconstriction, hypotension, intravascular platelet aggregation, endothelial disruption, and platelet and neutrophil diapedesis. These effects are followed within 1 h by an eosinophilic infiltration into the bronchial walls, which was also noted after the administration of antigen to passively sensitized guinea pigs. Bronchoconstriction and eosinophil infiltration are 2 major features of asthma, and selective bronchial eosinophilia characterizes late asthmatic reactions. We compared the histologic effects of PAF-acether 6 and 24 h after its intravenous injection with those of experimental passive anaphylactic shock, which is used as a model for asthma. Six hours after PAF-acether or antigen (ovalbumin) administration, a marked lung eosinophil infiltration, particularly in the bronchial walls, was noted, together with mucous plugs containing eosinophils in the bronchial lumen. Epithelial desquamation was followed after 24 h by mucous metaplasia of the bronchial epithelium. These effects were not observed when the inactive metabolite lyso-PAF was used. Our results agree fully with the suggestion that the eosinophil mediates the pathophysiology of bronchial asthma and releases materials toxic for the respiratory epithelium. Two PAF-acether antagonists (BN 52021 and WEB 2086) prevented the eosinophil infiltration triggered by PAF-acether and by antigen. When PAF-acether or ovalbumin were injected into guinea pigs after antiplatelet serum or prostacyclin, the eosinophil infiltration was significantly reduced, suggesting that platelets or another adenylate cyclase-sensitive cell are important for the subsequent PAF-acether-induced eosinophil infiltration. Our results support an essential role for PAF-acether in an experimental model of allergic asthma.
authors.affiliation: Unité de Pharmacologie cellulaire, Faculté de Médecine Necker-Enfants Malades, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Lellouch-Tubiana
authors.forename: J
authors.initials: J
authors.lastname: Lefort
authors.forename: M T
authors.initials: MT
authors.lastname: Simon
authors.forename: A
authors.initials: A
authors.lastname: Pfister
authors.forename: B B
authors.initials: BB
authors.lastname: Vargaftig
mesh_terms: D000485:Allergens / Q000494:pharmacology*; D000707:Anaphylaxis / Q000473:pathology; D000818:Animals; D000941:Antigens / Q000276:immunology; D001792:Blood Platelets / Q000166:cytology*; D001980:Bronchi / Q000473:pathology; D004804:Eosinophils / Q000166:cytology*; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D008168:Lung / Q000166:cytology* / Q000473:pathology; D008297:Male; D009092:Mucous Membrane / Q000473:pathology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010976:Platelet Count
chemical_list: D000485:Allergens; D000941:Antigens; D010972:Platelet Activating Factor; D011464:Epoprostenol