Pathways of anaphylaxis in the mouse.

Area of Science:

• Immunology
• Allergy Research
• Pathophysiology

Background:

• Anaphylaxis is typically mediated by IgE, FcepsilonRI, mast cells, and histamine.
• Alternative pathways involving IgG, FcgammaRIII, macrophages, platelets, and PAF are suggested by rodent studies.

Purpose of the Study:

• To determine the relative importance of classical (IgE-dependent) and alternative (IgG-dependent) anaphylaxis pathways.
• Investigate these pathways in a mouse model with mastocytosis and high IgE levels.

Main Methods:

• Used wild-type, IgE-deficient, FcepsilonRI-deficient, and mast cell-deficient mice.
• Induced anaphylaxis via antigen (goat IgG) or anti-IgE monoclonal antibody (mAb) challenge.
• Blocked or eliminated specific mediators, cell types, or Ig receptors prior to challenge.

Main Results:

• Both antigen and anti-IgE mAb induced similar anaphylaxis severity.
• Anti-IgE mAb-induced anaphylaxis required FcepsilonRI, mast cells, and histamine.
• Antigen-induced anaphylaxis was independent of mast cells and platelets, relying on FcgammaRIII, macrophages, and PAF.

Conclusions:

• Antigen-induced anaphylaxis in mice predominantly uses the IgG, FcgammaRIII, macrophage, and PAF pathway.
• This pathway is significant even in models with high IgE and mast cell responses.
• The IgG pathway's role in human anaphylaxis is plausible due to FcgammaRIII presence on human macrophages.