Pathways of immediate hypothermia and leukocyte infiltration in an adjuvant-free mouse model of anaphylaxis

J Allergy Clin Immunol. 2017 Feb;139(2):584-596.e10. doi: 10.1016/j.jaci.2016.05.047. Epub 2016 Jul 17.


Background: Conflicting results have been obtained regarding the roles of Fc receptors and effector cells in models of active systemic anaphylaxis (ASA). In part, this might reflect the choice of adjuvant used during sensitization because various adjuvants might differentially influence the production of particular antibody isotypes.

Objective: We developed an "adjuvant-free" mouse model of ASA and assessed the contributions of components of the "classical" and "alternative" pathways in this model.

Methods: Mice were sensitized intraperitoneally with ovalbumin at weekly intervals for 6 weeks and challenged intraperitoneally with ovalbumin 2 weeks later.

Results: Wild-type animals had immediate hypothermia and late-phase intraperitoneal inflammation in this model. These features were reduced in mice lacking the IgE receptor FcεRI, the IgG receptor FcγRIII or the common γ-chain FcRγ. FcγRIV blockade resulted in a partial reduction of inflammation without any effect on hypothermia. Depletion of monocytes/macrophages with clodronate liposomes significantly reduced the hypothermia response. By contrast, depletion of neutrophils or basophils had no significant effects in this ASA model. Both the hypothermia and inflammation were dependent on platelet-activating factor and histamine and were reduced in 2 types of mast cell (MC)-deficient mice. Finally, engraftment of MC-deficient mice with bone marrow-derived cultured MCs significantly exacerbated the hypothermia response and restored inflammation to levels similar to those observed in wild-type mice.

Conclusion: Components of the classical and alternative pathways contribute to anaphylaxis in this adjuvant-free model, with key roles for MCs and monocytes/macrophages.

Keywords: Fc receptors; Rodents; allergy; anaphylaxis; antibodies; inflammation; mast cells/basophils; monocytes/macrophages; mouse model; neutrophils.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic
  • Anaphylaxis / immunology*
  • Animals
  • Cell Movement*
  • Cells, Cultured
  • Complement Pathway, Alternative
  • Complement Pathway, Classical
  • Disease Models, Animal
  • Humans
  • Hypothermia / immunology*
  • Immunization
  • Leukocytes / immunology*
  • Macrophages / immunology*
  • Mast Cells / immunology*
  • Mast Cells / transplantation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, IgE / genetics
  • Receptors, IgE / metabolism
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism


  • Adjuvants, Immunologic
  • FcepsilonRIalpha protein, mouse
  • Fcgr3 protein, mouse
  • Fcgr4 protein, mouse
  • Receptors, IgE
  • Receptors, IgG