Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 123, Issue 2, Pages 342-351Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2008.11.004
Keywords
Peanut; C3a; complement; anaphylaxis; shock; macrophages; mart cells; basophils; platelet-activating factor; histamine
Categories
Funding
- US Department of Veterans Affairs and by National Institutes of Health [R21AI079947, R01GM083204, R01AI052099, AI059305, RO1AI073553, P30DK078392]
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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 beta-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. (J Allergy Clin Immunol 2009;123:342-51.)
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