Development of a Novel IgG₁ Anaphylaxis Mouse Model with Uniquely Characteristic Skin Manifestations Induced Through the FcγRIII-Histamine Pathway

ABSTRACT

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 IgG₁ anaphylaxis induced by the intravenous administration of two types of IgG₁ and a fluorescent dye-labeled antigen, as IgG₁ immune complex in HR-1 hairless mice. Subsequently, pharmacological analysis was used to investigate the underlying mechanisms of IgG₁ anaphylaxis in this established model.

Results

The novel IgG₁ 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 IgG₁ anaphylaxis. Basophils in the circulation and mast cells in the skin may participate in the development of IgG₁ 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 IgG₁ anaphylaxis. Further analysis of our model in addition to other models will lead to a broader analysis and understanding of the IgG₁ anaphylaxis mechanism.

KEYWORDS:

• Anaphylaxis
• basophils
• histamine
• immunoglobulin G
• mice

Acknowledgment

The authors thank Taylor & Francis Group (https://www.tandfeditingservices.com/) for editing a draft of this manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, KY, upon reasonable request.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.