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

Desquand, S.; Lefort, Jean; Dumarey, C.; Vargaftig, B.B.

doi:10.1111/j.1476-5381.1991.tb12234.x

Cited by 11 publications

(3 citation statements)

References 33 publications

(37 reference statements)

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“…One possible explanation for the large neutrophilic effect in our experiments involves the direct nasal instillation of the antigen. With a slightly different procedure of active sensitization, antigen challenge also caused a significant early increase in the number of eosinophils, without a change in neutrophil counts (Desquand et al, 1991). Thus, our present results support the concept that the signal for antigen-induced eosinophil and neutrophil recruitment involves different pathways, which are enhanced in sensitized guinea-pigs.…”

Section: Discussionsupporting

confidence: 84%

Interference of a neutrophil recruitment inhibitory factor upon the accumulation of inflammatory cells and airway hyperreactivity in sensitized guinea‐pigs after intranasal antigen challenge

Tavares‐Murta

Lefort

Cunha

et al. 1993

British J Pharmacology

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1 A neutrophil recruitment inhibitory factor (NRIF) recovered from the crude supernatant of lipopolysaccharide (LPS)-stimulated macrophages inhibited neutrophil migration following both intratracheal and intravenous administration of LPS, but did not alter the pattern of leukopenia/leucocytosis induced by intravenous LPS. 2 The correlation between airway infiltration by inflammatory cells and hyperreactivity in lungs from actively sensitized and challenged guinea-pigs was investigated by use of NRIF. 3 Increased eosinophil counts were found in the bronchoalveolar lavage fluid from guinea-pigs sensitized with 10 fig ovalbumin and challenged at day 14 by the intranasal administration of the antigen. The increase was evident 5 h after challenge and persisted at 24 h. Neutrophil numbers were also increased at this time. Pretreatment with NRIF suppressed the leucocyte increase in the bronchoalveolar lavage fluid. 4 Bronchoconstriction and histamine release induced by 3 ng PAF injected into the isolated lungs were increased in challenged guinea-pigs as compared to sensitized but unchallenged controls. Pretreatment of the animals with NRIF did not interfere with this response, but significantly reduced the bronchoconstriction induced by ovalbumin injection. 5Even though the increased number of inflammatory cells in bronchoalveolar lavage and airway hyperresponsiveness were concomitant, NRIF inhibited cellular infiltration but failed to alter airway hyperreactivity to PAF, demonstrating that these events may occur independently; Conversely, the inhibition of antigen-induced bronchoconstriction by NRIF suggests that this response is dependent upon the emigration of granulocytes.

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Section: Discussionsupporting

confidence: 84%

Interference of a neutrophil recruitment inhibitory factor upon the accumulation of inflammatory cells and airway hyperreactivity in sensitized guinea‐pigs after intranasal antigen challenge

Tavares‐Murta

Lefort

Cunha

et al. 1993

British J Pharmacology

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“…In this study, the varied responsiveness of AMs to tachykinins in vitro follows a sensitization procedure which, according to Garcez Do Carmo et al (1986), Pretolani et al (1989) and Desquand et al (1991), causes serum levels of both IgG and IgE to be significantly enhanced. AMs obtained from actively sensitized guinea-pigs have been shown to possess an impaired adenylate cyclase activity, conflicting results being reported (Bachelet et al, 1989;Beusenberg et al, 1989;.…”

Section: Discussionmentioning

confidence: 99%

Enhanced responsiveness of ovalbumin‐sensitized guinea‐pig alveolar macrophages to tachykinins

Brunelleschi

Parenti

Ceni

et al. 1992

British J Pharmacology

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1 We have evaluated the ability of substance P (SP), neurokinin A (NKA) and the selective NK2 receptor agonist [P-Ala8]-NKA(4-10) to induce superoxide anion (02-) production and prostanoid (prostaglandin E2, thromboxane B2) release from alveolar macrophages (AMs) isolated from control or actively sensitized guinea-pigs. 2 The dose-response curves for NKA and SP were shifted to the left (three orders and one order of magnitude, respectively) in AMs isolated from sensitized animals, with no variation in maximal effects. 3 By evaluating the effects of [P-Ala8]-NKA(4-10), we observed that not only was the concentrationresponse curve shifted to the left in both the functional parameters examined, but also maximal effects were significantly enhanced in AMs isolated from sensitized guinea-pigs. 4 This varied responsiveness seems to be specific for tachykinins, as it was not reproduced by another AM stimulant, the bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP).5 Only small amounts of P-glucuronidase were released following tachykinin or ovalbumin stimulation both in control and sensitized AMs. 6 These results indicate that AMs isolated from sensitized guinea-pigs show an increased responsiveness to NK2 receptor stimulation and further stress the role played by AMs in allergic lung diseases.

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“…In addition, Pretolani et al (1989) showed that BN 52021 and WEB 2086, which inhibit PAF-induced effects in isolated lungs from non-immunized or from immunized but unboosted guinea-pigs, failed to do so when the lungs are from boosted guinea-pigs. Furthermore, intratracheal administration of antigen caused a marked increase of the number of eosinophils in bronchoalveolar lavage fluids in boosted, but not in unboosted guinea-pigs (Desquand et al 1991). The efficacy of these PAF antagonists against anaphylactic bronchopulmonary responses in unboosted guinea-pigs only, suggests that the booster injection of antigen modified the lung responsiveness and PAF appears to be relevant for antigen-induced bronchopulmonary responses in unboosted animals, but loses its major role following the booster injection (Desquand et al 1991).…”

Section: Discussionmentioning

confidence: 99%

The effect of the selective PAF antagonist CIS-19 on PAF- and antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity in guinea-pigs

Lin

Ishii

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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We investigated the effects of a novel platelet-activating factor (PAF) receptor antagonist, CIS-19 [cis-2-(3, 4-dimethoxyphenyl)-6-isopropoxy-7-methoxy-1-(N-methyl-formamido)-1, 2, 3, 4-tetrahydronaphthalene], on PAF-, histamine-, substance P- and antigen-induced bronchoconstriction and microvascular leakage, as well as PAF- and antigen-induced bronchial hyperreactivity to methacholine in urethane-anesthetized guinea-pigs. Administration of CIS-19 (0.5-5 mg/kg, i.v.) inhibited the increase in lung resistance induced by PAF (30 ng/kg, i.v.) in a dose-dependent manner, but failed to inhibit the increase induced by histamine (30 micrograms/kg, i.v.) or substance P (6.5 micrograms/kg, i.v.). CIS-19 (5 mg/kg, i.v.) did not inhibit the increase in lung resistance induced by ovalbumin (2 mg/kg, i.v.) in actively sensitized guinea-pigs. PAF (30 ng/kg, i.v.)-induced microvascular leakage, measured by the extravasation of Evans blue dye, was dose-dependently inhibited by CIS-19 (0.5-5 mg/kg, i.v.) in the trachea, main bronchi and intrapulmonary airways, but it did not affect histamine (30 micrograms/kg, i.v.)- or substance P (6.5 micrograms/kg, i.v.)-induced microvascular leakage at all airway levels. CIS-19 (2.5 and 5 mg/kg) did not affect ovalbumin (2 mg/kg, i.v.)-induced microvascular leakage in all airway levels in actively sensitized guinea-pigs, CIS-19 (2.5 and 5 mg/kg, i.v.) significantly inhibited PAF-induced enhancement of the bronchial response to methacholine, but had no effect on ovalbumin (0.05 mg/kg, i.v.)-induced bronchial hyperreactivity in actively sensitized guinea-pigs. It is concluded that CIS-19 is a potent PAF receptor antagonist which inhibits PAF- but not antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity. These results suggest that PAF plays little or no role in early airway responses following antigen challenge.

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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

Cited by 11 publications

References 33 publications

Interference of a neutrophil recruitment inhibitory factor upon the accumulation of inflammatory cells and airway hyperreactivity in sensitized guinea‐pigs after intranasal antigen challenge

Interference of a neutrophil recruitment inhibitory factor upon the accumulation of inflammatory cells and airway hyperreactivity in sensitized guinea‐pigs after intranasal antigen challenge

Enhanced responsiveness of ovalbumin‐sensitized guinea‐pig alveolar macrophages to tachykinins

The effect of the selective PAF antagonist CIS-19 on PAF- and antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity in guinea-pigs

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