title: IgE antibodies, FcεRIα, and IgE-mediated local anaphylaxis can limit snake venom toxicity.
abstract: BACKGROUND
  Type 2 cytokine-related immune responses associated with development of antigen-specific IgE antibodies can contribute to pathology in patients with allergic diseases and to fatal anaphylaxis. However, recent findings in mice indicate that IgE also can enhance defense against honeybee venom.
  
  
  OBJECTIVE
  We tested whether IgE antibodies, IgE-dependent effector mechanisms, and a local anaphylactic reaction to an unrelated antigen can enhance defense against Russell viper venom (RVV) and determined whether such responses can be influenced by immunization protocol or mouse strain.
  
  
  METHODS
  We compared the resistance of RVV-immunized wild-type, IgE-deficient, and Fcer1a-deficient mice after injection of a potentially lethal dose of RVV.
  
  
  RESULTS
  A single prior exposure to RVV enhanced the ability of wild-type mice, but not mice lacking IgE or functional FcεRI, to survive challenge with a potentially lethal amount of RVV. Moreover, IgE-dependent local passive cutaneous anaphylaxis in response to challenge with an antigen not naturally present in RVV significantly enhanced resistance to the venom. Finally, we observed different effects on resistance to RVV or honeybee venom in BALB/c versus C57BL/6 mice that had received a second exposure to that venom before challenge with a high dose of that venom.
  
  
  CONCLUSIONS
  These observations illustrate the potential benefit of IgE-dependent effector mechanisms in acquired host defense against venoms. The extent to which type 2 immune responses against venoms can decrease pathology associated with envenomation seems to be influenced by the type of venom, the frequency of venom exposure, and the genetic background of the host.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Philipp
authors.initials: P
authors.lastname: Starkl
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Thomas
authors.initials: T
authors.lastname: Marichal
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gaudenzio
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Laurent Lionel
authors.initials: LL
authors.lastname: Reber
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sibilano
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Mindy
authors.initials: M
authors.lastname: Tsai
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, Calif; Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, Calif. Electronic address: sgalli@stanford.edu.
authors.forename: Stephen Joseph
authors.initials: SJ
authors.lastname: Galli
mesh_terms: D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D001514:Bee Venoms / Q000276:immunology; D015550:Cell Degranulation; D005260:Female; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology / Q000502:physiology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology*; D014757:Viper Venoms / Q000276:immunology*
chemical_list: D001514:Bee Venoms; C579617:FcepsilonRIalpha protein, mouse; D017455:Receptors, IgE; D014757:Viper Venoms; D007073:Immunoglobulin E
keywords: Acquired resistance; Daboia russelii; FcεRIα; IgE; Russell viper; allergy; honeybee; mast cells; toxin hypothesis; type 2 immunity; venom