The effect of the selective PAF antagonist BN 52021 on PAF- and antigen-induced bronchial hyper-reactivity and eosinophil accumulation.
Sensitised guinea-pigs were exposed to an aerosol of ovalbumin (100-500 micrograms/ml) and normal animals were exposed to an aerosol of platelet activating factor (PAF) (250-1000 micrograms/ml). Twenty-four hours later, bronchial reactivity was assessed by measurement of air overflow in response to i.v. histamine or acetylcholine using the Konsett-Rossler technique. Additionally, bronchoalveolar lavage was performed by washing the lungs with 10 ml of 0.9% saline and differential counts obtained to assess the ability of PAF and antigen to elicit pulmonary inflammatory cell recruitment. Both PAF and antigen exposure produced a dose-related increase in bronchial reactivity, while treatment with the vehicle (either 0.25% bovine serum albumin or 0.9% saline) had no effect on airway responsiveness. Furthermore, both PAF and antigen exposure produced a selective accumulation of eosinophils into the airways. There was no significant change in the number of neutrophils, macrophages or lymphocytes. The selective PAF antagonist BN52021 inhibited both the development of bronchial hyper-reactivity and the eosinophil influx into the airways induced by PAF or antigen exposure. These observations suggest that PAF has a central role to play in the antigen induced eosinophil accumulation and subsequent bronchial hyper-reactivity.
Coyle
A J
AJ
Department of Pharmacology, King's College, London University, England.
Urwin
S C
SC
Page
C P
CP
Touvay
C
C
Villain
B
B
Braquet
P
P
D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000209:etiology / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid; D004224:Diterpenes; D004804:Eosinophils / Q000187:drug effects*; D046934:Ginkgolides; D006168:Guinea Pigs; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*
D000941:Antigens; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D010047:Ovalbumin; C045856:ginkgolide B