A possible role for PAF in allergen-induced late responses: modification by a selective antagonist.
We determined whether platelet-activating factor (PAF) plays a role in allergen-induced airway responses by studying the effects of a selective PAF antagonist WEB-2086 on antigen-induced early and late airway responses in allergic sheep. In seven sheep, inhaled Ascaris suum produced significant early (282%) and late (176%) increases in specific lung resistance (sRL). WEB-2086 (1 mg/kg iv) given 20 min before antigen challenge did not affect the early response, but the peak late increase in sRL was only 37% over base line (P less than 0.05 vs. control). To study the mechanism by which PAF contributes to antigen-induced responses, we evaluated the effects of pharmacological probes on PAF-induced bronchoconstriction. Inhaled PAF (dose range 75-700 micrograms) caused reproducible (r = 0.781, P less than 0.05) increases in sRL in eight sheep. The PAF-induced bronchoconstriction was blocked by WEB-2086 (1 mg/kg iv) and by the leukotriene antagonist FPL-55712 (30 mg by aerosol); however, neither the cyclooxygenase blocker indomethacin (2 mg/kg iv) nor the histamine H1-antagonist chlorpheniramine (2 mg/kg iv) blocked the PAF response. WEB-2086, however, did not block bronchoconstriction induced by aerosol leukotriene D4, indicating that PAF acts indirectly through leukotrienes. Finally, we determined whether PAF could induce late airway responses. Inhaled PAF produced an immediate increase in sRL in all seven sheep tested, but late airway responses were observed in only three of the seven sheep.(ABSTRACT TRUNCATED AT 250 WORDS)
Abraham
W M
WM
Division of Pulmonary Diseases, Mount Sinai Medical Center, Miami Beach, Florida 33140.
Stevenson
J S
JS
Garrido
R
R
D000336:Aerosols; D000485:Allergens; D000818:Animals; D000947:Antigens, Helminth; D001200:Ascaris; D001249:Asthma / Q000503:physiopathology; D001381:Azepines / Q000494:pharmacology*; D002744:Chlorpheniramine / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004195:Disease Models, Animal; D006968:Hypersensitivity, Delayed; D006969:Hypersensitivity, Immediate; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D012016:Reference Values; D013189:SRS-A / Q000037:antagonists & inhibitors; D012756:Sheep; D014227:Triazines / Q000494:pharmacology*; D014230:Triazoles
D000336:Aerosols; D000485:Allergens; D000947:Antigens, Helminth; D001381:Azepines; D002867:Chromones; D010972:Platelet Activating Factor; D013189:SRS-A; D014227:Triazines; D014230:Triazoles; C052518:WEB 2086; D002744:Chlorpheniramine; C006312:FPL 55712; D007213:Indomethacin