Peanuts can contribute to anaphylactic shock by activating complement

Marat Khodoun, Richard Strait, Tatyana Orekov, Simon Hogan, Hajime Karasuyama, De'Broski R. Herbert, Jörg Köhl, Fred D. Finkelman*

*Corresponding author for this work
90 Citations (Scopus)


Background: Peanut allergy is the most common food-related cause of lethal anaphylaxis and, unlike other food allergies, typically persists into adulthood. Resistance to digestion and dendritic cell activation by the major peanut allergen Ara h 1 are reported to contribute to its allergenicity. Objective: We sought to evaluate whether peanut molecules might also promote anaphylaxis through an innate immune mechanism. Methods: Naive mice were treated with a β-adrenergic receptor antagonist and long-acting IL-4 to increase sensitivity to vasoactive mediators and injected with peanut extract (PE). Shock was detected and quantified by means of rectal thermometry. Gene-deficient mice and specific antagonists were used to determine the roles of specific cell types, complement, Fc receptors, and vasoactive mediators in shock pathogenesis. Results: PE induces dose-dependent shock. PE activates complement in vivo in mice and in vitro in mice and human subjects. C3a and, to a lesser extent, stimulatory immunoglobulin receptors contribute to PE-induced shock. PE-induced shock depends more on macrophages and basophils than on mast cells. Platelet-activating factor and, to a lesser extent, histamine contribute to PE-induced shock. PE induces shock in the absence of the adaptive immune system. LPS contamination is not responsible for PE-induced shock. PE and IgE-mediated mast cell degranulation synergistically induce shock. Tree nuts have similar effects to PE, and skim milk and egg white do not. Conclusion: Peanuts can contribute to shock by causing production of C3a, which stimulates macrophages, basophils, and mast cells to produce platelet-activating factor and histamine.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
Issue number2
Pages (from-to)342-351
Number of pages10
Publication statusPublished - 01.02.2009


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