Development of a Novel IgG Anaphylaxis Mouse Model with Uniquely Characteristic Skin Manifestations Induced Through the FcγRIII-Histamine Pathway.

Background: Studies of passive anaphylaxis, in which mouse immunoglobulin G (IgG) and its antigens are administered to mice, believe that platelet-activating factor (PAF) is more important than histamine and that basophils or macrophages are primarily involved. However, the full extent of IgG-dependent anaphylaxis is still unclear; that is, little agreement has been reached about the mechanism.

Methods: First, we established the novel model of IgG anaphylaxis induced by the intravenous administration of two types of IgG and a fluorescent dye-labeled antigen, as IgG immune complex in HR-1 hairless mice. Subsequently, pharmacological analysis was used to investigate the underlying mechanisms of IgG anaphylaxis in this established model.

Results: The novel IgG anaphylaxis model can induce the IgG-induced Anaphylaxis-dependent Spotted Distribution of fluorescently labeled Immune complexes in the Skin, named "G-ASDIS". Moreover, this model was triggered primarily by the FcγRIII-dependent histamine release, which is different from the conventional model in which PAF was involved in the development of IgG anaphylaxis. Basophils in the circulation and mast cells in the skin may participate in the development of IgG anaphylaxis and increased G-ASDIS.

Conclusion: Our results propose that the novel axis, namely the FcγRIII-basophils and/or mast cell-histamine pathway, is important for IgG anaphylaxis. Further analysis of our model in addition to other models will lead to a broader analysis and understanding of the IgG anaphylaxis mechanism.