Interference of BN 52021, an antagonist of PAF, with different forms of active anaphylaxis in the guinea-pig: importance of the booster injection.
1. BN 52021, an antagonist of platelet activating factor (PAF), was inactive against bronchoconstriction in guinea-pigs sensitized with low amounts of ovalbumin (OA) injected twice, at a 14 day interval and challenged i.v. 7 days later. 2. Serum IgG titers increased for 7 weeks after the booster injection at day 14 and returned to low levels at day 96. 3. Administered by the intratracheal (i.t.) route at 1 mg, BN 52021 failed to inhibit bronchoconstriction induced by the i.t. administration of OA to guinea-pigs tested 7, 28, 56 and 84 days after the booster injection, even when the titers of circulating IgG had declined with time. BN 52021 was also inactive against bronchoconstriction in guinea-pigs boosted at day 98 and tested 7 days later and against contractions and thromboxane (Tx) B2 and histamine release induced by OA-challenged parenchymal lung strips from the boosted guinea-pigs. 4. Sensitized unboosted guinea-pigs displayed reduced IgG serum titers. Used 21 or 70 days after the sensitizing injection, they did develop bronchoconstriction upon the i.t. instillation of OA, which was blocked by BN 52021. The latter also inhibited OA-induced contractions of lung parenchymal strips from these unboosted guinea-pigs. 5. When boosted and non-boosted guinea-pigs received OA i.t. and bronchoalveolar lavage fluid was collected 10 min later, the number of eosinophils increased markedly in boosted, but not in non-boosted guinea-pigs. 6. The booster injection of antigen thus modifies the response of the lung and PAF appears to be relevant for antigen-induced bronchoconstriction in unboosted animals, but loses its major role following the booster injection.
Desquand
S
S
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur- Institut National de la Santé et de la Recherche Médicale, Paris, France.
Lefort
J
J
Dumarey
C
C
Vargaftig
B B
BB
D000707:Anaphylaxis / Q000517:prevention & control*; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D004224:Diterpenes; D005260:Female; D046934:Ginkgolides; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D007117:Immunization, Secondary; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D013929:Thromboxane B2 / Q000096:biosynthesis
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D013929:Thromboxane B2; D010047:Ovalbumin; C045856:ginkgolide B