Blockade of platelet-activating factor (PAF) prevents peanut-induced anaphylaxis in mice

Platelet-activating factor, also known as a PAF, is a potent phospholipid activator and mediator of platelet aggregation, inflammation, and anaphylaxis. PAF is produced by a variety of cells, including neutrophils, basophils, platelets, and endothelial cells. The PAF receptor is a G-protein coupled receptor which binds platelet-activating factor.

Platelet-Activating Factor (PAF). Image source: Wikipedia, GNU Free Documentation License.

Food anaphylaxis is an acute and life-threatening systemic allergic reaction. Fatality registries place peanut as the most common culprit of fatal and near-fatal reactions in North America.

The authors investigated the impact of blocking mast cell mediators in a mouse model of peanut-induced anaphylaxis.

One week after the last sensitization, separate groups of mice were treated with either a (1) 5-lypoxygenase inhibitor, (2) a platelet-activating factor (PAF) receptor antagonist, (3) histamine receptor antagonists, or (4) a PAF receptor antagonist along with histamine receptor antagonists before peanut challenge.

Treatment targeting either leukotrienes or histamine alone had no beneficial effects. In contrast, PAF antagonism significantly attenuated the magnitude and duration of the anaphylactic reactions. Particularly, it prevented severe reactions.

Notably, combined blockade of PAF and histamine had a clearly greater beneficial effect. In fact, all but 1 mouse developed mild, if any, anaphylactic reactions.

The authors concluded that a combination therapy blocking both PAF and histamine markedly reduces the severity of peanut-induced anaphylaxis, and thus it may be a potential life-saving therapeutic approach in food-induced anaphylaxis.

Concurrent blockade of platelet-activating factor and histamine prevents life-threatening peanut-induced anaphylactic reactions. Arias K, Baig M, Colangelo M, Chu D, Walker T, Goncharova S, Coyle A, Vadas P, Waserman S, Jordana M. J Allergy Clin Immunol. 2009 Apr 29.
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