The effect of the selective PAF antagonist WEB 2170 on PAF and antigen induced airway hyperresponsiveness and eosinophil infiltration.
Exposure of normal guinea pigs to an aerosol of PAF induced an increase in airway responsiveness to i.v. histamine, 24 h and 48 h post challenge compared to animals that received BSA alone. There was no significant alteration in airway responsiveness 1 h, 4 h or 72 h after PAF challenge. Exposure of actively sensitised guinea pigs to an aerosol of ovalbumin induced airway hyperresponsiveness to i.v. histamine, 24 h post challenge. PAF induced a selective increase in the percentage of eosinophils in bronchoalveolar lavage fluid 24 h after challenge, that persisted for at least 72 h post challenge. No significant increase in eosinophils was noted 1-4 h after PAF exposure. Antigen challenge of actively sensitised guinea pigs induced a significant increase in the percentage of eosinophils recovered in BAL fluid 24 h post challenge. Pretreatment of both normal and sensitised guinea pigs with the selective PAF antagonist WEB 2170 significantly inhibited both airway hyperresponsiveness and airway eosinophilia 24 h post challenge with aerosol PAF or allergen. These results further support the suggestion that PAF may play a central role in allergen induced eosinophil infiltration and airway hyperresponsiveness in the guinea pig.
Seeds
E A
EA
Department of Pharmacology, King's College, University of London, U.K.
Coyle
A J
AJ
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C P
CP
D000336:Aerosols; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D001381:Azepines / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D004334:Drug Administration Schedule; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D006168:Guinea Pigs; D006632:Histamine / Q000008:administration & dosage; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology*
D000336:Aerosols; D000941:Antigens; D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; D006632:Histamine; C063964:bepafant