The Role of PAF-Acether in Anaphylaxis Demonstrated with the Use of the Antagonist BN 52021

Braquet, P.; Guinot, Philippe; Touvay, Caroline

doi:10.1007/978-3-0348-7451-9_8

Cited by 4 publications

(1 citation statement)

References 54 publications

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“…We then tested the effect of endothelium-specific Gα q /Gα 11 and Gα 12 /Gα 13 deficiency on the systemic response to PAF, which is thought to be a critical mediator of anaphylactic shock (32–34). i.v.…”

Section: Resultsmentioning

confidence: 99%

Anaphylactic shock depends on endothelial Gq/G11

Korhonen

Fißlthaler

Moers

et al. 2009

Journal of Experimental Medicine

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Anaphylactic shock is a severe allergic reaction involving multiple organs including the bronchial and cardiovascular system. Most anaphylactic mediators, like platelet-activating factor (PAF), histamine, and others, act through G protein–coupled receptors, which are linked to the heterotrimeric G proteins Gq/G11, G12/G13, and Gi. The role of downstream signaling pathways activated by anaphylactic mediators in defined organs during anaphylactic reactions is largely unknown. Using genetic mouse models that allow for the conditional abrogation of Gq/G11- and G12/G13-mediated signaling pathways by inducible Cre/loxP-mediated mutagenesis in endothelial cells (ECs), we show that Gq/G11-mediated signaling in ECs is required for the opening of the endothelial barrier and the stimulation of nitric oxide formation by various inflammatory mediators as well as by local anaphylaxis. The systemic effects of anaphylactic mediators like histamine and PAF, but not of bacterial lipopolysaccharide (LPS), are blunted in mice with endothelial Gαq/Gα11 deficiency. Mice with endothelium-specific Gαq/Gα11 deficiency, but not with Gα12/Gα13 deficiency, are protected against the fatal consequences of passive and active systemic anaphylaxis. This identifies endothelial Gq/G11-mediated signaling as a critical mediator of fatal systemic anaphylaxis and, hence, as a potential new target to prevent or treat anaphylactic reactions.

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Section: Resultsmentioning

confidence: 99%

Anaphylactic shock depends on endothelial Gq/G11

Korhonen

Fißlthaler

Moers

et al. 2009

Journal of Experimental Medicine

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Separate induction of human blood platelet aggregation or cytotoxicity by different concentrations of PAF-acether and thrombin

et al. 1992

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Using decreasing concentrations of PAF-acether or thrombin, it was possible to observe on human platelets, first, aggregation, classically associated to activation, then , below a threshold, cytotoxicity towards Schistosoma mansoni larvae, proposed here as stimulation. These two activities appeared as distinct and antithetic. However, their induction might be the consequence of triggering of the same receptors with different intensity, since PAF-induced, but not thrombin-induced, cytotoxicity could be inhibited with specific PAF-antagonists BN 52021 and BN 52024 also known to inhibit PAF-induced aggregation. These results give credit to the hypothesis that haemostatic and cytotoxic properties of platelets are two distinct functions of these blood elements.

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