Interference of PAF-acether antagonists with the effects of PAF itself and of anaphylactic shock in and guinea-pig bronchopulmonary

Lagente, Vincent; Desquand, S.; Randon, Jacques; Lefort, Jean; Vargaftig, B.B.

doi:10.1016/0090-6980(85)90047-4

Cited by 12 publications

(5 citation statements)

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“…Our claim that the booster injection determines whether the anaphylactic bronchoconstriction is or is not suppressed by BN 52021 explains the initial disappointing results obtained with PAF antagonists used against active anaphylactic bronchoconstriction and negates previous conclusions that PAF is not involved in active anaphylaxis (Detsouli et al, 1985;Lagente et al, 1985;Danko et al, 1988). This finding can probably be generalized.…”

Section: Discussioncontrasting

confidence: 48%

“…administration of BN 52021 to guinea-pigs of group 14 + 7, 30min before the instillation of OA failed to inhibit bronchoconstriction. In addition, BN 52021 also failed here to reduce the contractions and the TxB2 formation and histamine liberation by OA-challenged parenchymal lung strips (present results), as well as the release of mediators from perfused lungs provided by boosted guinea-pigs of group 14 + 7 (Lagente et al, 1985). It is thus clear that BN 52021 is inactive against anaphylaxis of guinea-pigs of group 14 + 7, irrespective of the lung preparation used and of the route of administration of the antigen.…”

Section: Discussionmentioning

confidence: 72%

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Interference of BN 52021, an antagonist of PAF, with different forms of active anaphylaxis in the guinea‐pig: importance of the booster injection

Desquand

Lefort

Dumarey

et al. 1991

British J Pharmacology

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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.

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Section: Discussioncontrasting

confidence: 48%

Section: Discussionmentioning

confidence: 72%

Interference of BN 52021, an antagonist of PAF, with different forms of active anaphylaxis in the guinea‐pig: importance of the booster injection

Desquand

Lefort

Dumarey

et al. 1991

British J Pharmacology

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“…Among the different inflammatory mediators, the involvement of platelet activating factor (PAF) in allergic pulmonary reactions was first suggested by the demonstration that it induced a marked bronchoconstriction unrelated to the production of cyclo-oxygenase metabolites in the guineapig [2]. Furthermore, a marked inhibition of the bronchopulmonary and haematological alterations during anaphylactic shock in the guinea-pig by a specific PAF receptor antagonist was described for the ginkgolide compound extracted from Oinkgo biloba L., BN 52021 [3][4][5][6]. Inhibitory activities by PAF antagonists on the antigen-induced bronchopulmonary alterations was also observed with the analog of PAF, Ro 19-3704 [7] or the triazolobenzodiazepine WEB 2086 [8.9].…”

Section: Introductionmentioning

confidence: 99%

Effects of the platelet activating factor antagonists BN 52021 and BN 50730 on antigen‐induced bronchial hyperresponsiveness and eosinophil infiltration in lung from sensitized guinea‐pigs

Lagente¹,

Boichot²,

Carré³

et al. 1993

Clin Experimental Allergy

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The involvement of platelet activating factor (PAF) in antigen-induced bronchial hyperresponsiveness was investigated by the use of the PAF antagonists BN 52021 and BN 50730, in a guinea-pig model where sensitization and challenge were performed by aerosol. Male Hartley guinea-pigs were sensitized by two aerosol exposures at 48 hr intervals to a 0.9% NaCl solution (saline) containing 2 mg/ml ovalbumin for 30 min. Fifteen to 20 days later, guinea-pigs were challenged by exposure to five successive aerosols of increasing concentrations of ovalbumin (OA) or respectively, 10 microg/ml, 100 microg/ml, 1 mg/ml, 5 mg/ml and 10 mg/ml for 15 min each, or saline alone. Three to four hr and 18-24 hr after the aerosol challenge the guinea-pigs were prepared for recording of bronchopulmonary response and aerosol administrations were then generated with an ultrasonic nebulizer. The bronchopulmonary responses induced by successive 1-min aerosol bursts of acetylcholine (ACh) was assessed. As compared with saline-challenged guinea-pigs, an enhanced bronchopulmonary response to aerosol administration of cumulative doses of ACh was observed, 3-4 hr and 18-24 hr post-ovalbumin challenge. When the sensitized guinea-pigs were pretreated 1 hr before ovalbumin exposure with BN 52021 or BN 50730 (25 mg/kg, per os), a significant inhibition of the increase in the bronchopulmonary response to ACh was observed, both at 3-4 hr and 18-24 hr. Furthermore, when guinea-pigs were treated 3-4 hr after the ovalbumin exposure with BN 52021 or BN 50730, a significant inhibition of the hyperresponsiveness to ACh was recorded at 18-24 hr. A marked accumulation of eosinophils in the peribronchial regions was observed on histological preparations of lung specimens collected 4 hr or 24 hr after ovalbumin exposure. Pretreatment of the guinea-pigs by BN 50730 or BN 52021 did not modify the eosinophil accumulation in the peribronchial area. No significant difference in the number of eosinophils collected in the bronchoalveolar lavage fluid is observed, 24 hr post-ovalbumin challenge, under the pretreatment with BN 52021 or BN 50730. Pretreatment of guinea-pigs by BN 50730 or BN 52021 significantly reduced the PAF-induced (100 microg/ml) increase in eosinophil number in the peribronchial area. By contrast, they did not inhibit the eosinophilia induced by aerosol administration of LTB4 (5 microg/ml). These results suggest that the bronchial hyperresponsiveness observed in this study is associated with eosinophil accumulation in the lung. The potent inhibition of the bronchial hyperresponsiveness by the two unrelated antagonists of PAF suggests that the lipid mediator is involved in its triggering and duration, but not in the eosinophil infiltration.

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“…Thus, BN 52021 blocked BC of passive homologous anaphylactic shock, inhibition being re moved when the guinea pigs were pretreated with pro pranolol, which did not prevent the anti-PAF effect, but did suppress antagonism to anaphylactic BC [13,32]. Contradictory results have been reported con cerning the effect of BN 52021 on systemic anaphy lactic BC [33,34], These discrepancies are probably related to the fact that the two groups do not use the same protocol of active sensitization shock. In the present study, anaphylactic BC was only blocked when BN 52021 was associated to mepyramine and FPL 55712.…”

Section: Discussionmentioning

confidence: 43%

Antigen-Induced Bronchopulmonary Alterations in the Guinea Pig: A New Model of Passive Sensitization Mediated by Mouse IgE Antibodies

Desquand

Lefort

Liu³

et al. 1989

Int Arch Allergy Immunol

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A selective model to study the IgE-mediated anaphylactic bronchoconstriction (BC) in the guinea pig is needed, since human asthma involves mainly this class of antibody. However, most procedures presently available for passive homologous or active sensitization lead to responses which are mediated both by IgE and IgG antibodies. In this study, we developed an anaphylactic model in which guinea pigs are passively sensitized with mouse ascitic fluid containing dinitrophenol (DNP)-specific IgE antibodies. Challenge of sensitized animals with DNP coupled to bovine serum albumin evokes a bronchoconstrictor response that is maximal 5 h after sensitization. The resulting anaphylactic BC is not blocked by the H₁ histamine antagonist mepyramine, by the peptido-leukotriene antagonist FLP 55712 nor by the platelet-activating factor antagonist BN 52021 alone. However, when the sensitized animals are pretreated with the three drugs in combination, significantly reduced BC was observed upon challenge with the antigen. This latter result indicates that IgE-dependent BC involves the participation of different mediators, a characteristic shared in common with allergic asthma in human.

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Interference of PAF-acether antagonists with the effects of PAF itself and of anaphylactic shock in and guinea-pig bronchopulmonary

Cited by 12 publications

References 0 publications

Interference of BN 52021, an antagonist of PAF, with different forms of active anaphylaxis in the guinea‐pig: importance of the booster injection

Interference of BN 52021, an antagonist of PAF, with different forms of active anaphylaxis in the guinea‐pig: importance of the booster injection

Effects of the platelet activating factor antagonists BN 52021 and BN 50730 on antigen‐induced bronchial hyperresponsiveness and eosinophil infiltration in lung from sensitized guinea‐pigs

Antigen-Induced Bronchopulmonary Alterations in the Guinea Pig: A New Model of Passive Sensitization Mediated by Mouse IgE Antibodies

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