Peanuts can contribute to anaphylactic shock by activating complement

J Allergy Clin Immunol. 2009 Feb;123(2):342-51. doi: 10.1016/j.jaci.2008.11.004. Epub 2009 Jan 3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Allergens / immunology
  • Anaphylaxis / etiology
  • Anaphylaxis / immunology*
  • Animals
  • Arachis / immunology*
  • Arachis / metabolism
  • Basophils / immunology
  • Basophils / metabolism
  • Cell Degranulation / immunology
  • Chymases / blood
  • Complement Activation / immunology*
  • Complement C3a / genetics
  • Complement C3a / immunology*
  • Complement C3a / metabolism
  • Histamine / immunology
  • Histamine / metabolism
  • Humans
  • Immunoglobulin E / blood
  • Interleukin-4 / pharmacology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Peanut Hypersensitivity / immunology*
  • Peanut Hypersensitivity / metabolism
  • Platelet Activating Factor / immunology
  • Platelet Activating Factor / metabolism
  • Propranolol / pharmacology
  • Receptors, IgG / genetics
  • Receptors, IgG / immunology
  • Receptors, IgG / metabolism
  • Toll-Like Receptors / immunology
  • Toll-Like Receptors / metabolism


  • Adrenergic beta-Antagonists
  • Allergens
  • Platelet Activating Factor
  • Receptors, IgG
  • Toll-Like Receptors
  • Interleukin-4
  • Immunoglobulin E
  • Complement C3a
  • Histamine
  • Propranolol
  • Chymases
  • Mcpt1 protein, mouse