Basophils play a pivotal role in immunoglobulin-G-mediated but not immunoglobulin-E-mediated systemic anaphylaxis

Immunity. 2008 Apr;28(4):581-9. doi: 10.1016/j.immuni.2008.02.008. Epub 2008 Mar 13.

Abstract

Anaphylaxis is an acute, severe, and potentially fatal systemic allergic reaction. Immunoglobulin E (IgE), mast cells, and histamine have long been associated with anaphylaxis, but an alternative pathway mediated by IgG has been suggested to be more important in the elicitation of anaphylaxis. Here, we showed that basophils, the least common blood cells, were dispensable for IgE-mediated anaphylaxis but played a critical role in IgG-mediated, passive and active systemic anaphylaxis in mice. In vivo depletion of basophils but not macrophages, neutrophils, or NK cells ameliorated IgG-mediated passive anaphylaxis and rescued mice from death in active anaphylaxis. Upon capture of IgG-allergen complexes, basophils released platelet-activating factor (PAF), leading to increased vascular permeability. These results highlight a pivotal role for basophils in vivo and contrast two major, distinct pathways leading to allergen-induced systemic anaphylaxis: one mediated by basophils, IgG, and PAF and the other "classical" pathway mediated by mast cells, IgE, and histamine.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / administration & dosage
  • Allergens / immunology
  • Anaphylaxis / immunology*
  • Anaphylaxis / pathology
  • Animals
  • Basophils / immunology*
  • Basophils / metabolism
  • Basophils / pathology
  • Immunoglobulin E / physiology*
  • Immunoglobulin G / physiology*
  • Macrophages / immunology
  • Mast Cells / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Platelet Activating Factor / physiology
  • Receptors, IgG / physiology
  • Signal Transduction / immunology

Substances

  • Allergens
  • Immunoglobulin G
  • Platelet Activating Factor
  • Receptors, IgG
  • Immunoglobulin E
  • Ovalbumin