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

• Published in: Immunological investigations 2023-01, Vol.52 (1), p.83-103
• Main Authors: Terashi, Masato, Yamaki, Kouya, Koyama, Yutaka
• Format: Article
• Language: English
• Subjects: Anaphylaxis; basophils; histamine; immunoglobulin G; mice
• ISSN: 0882-0139; 1532-4311
• DOI: 10.1080/08820139.2022.2130799

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. First, we established the novel model of IgG 1 anaphylaxis induced by the intravenous administration of two types of IgG 1 and a fluorescent dye-labeled antigen, as IgG 1 immune complex in HR-1 hairless mice. Subsequently, pharmacological analysis was used to investigate the underlying mechanisms of IgG 1 anaphylaxis in this established model. The novel IgG 1 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 1 anaphylaxis. Basophils in the circulation and mast cells in the skin may participate in the development of IgG 1 anaphylaxis and increased G-ASDIS. Our results propose that the novel axis, namely the FcγRIII-basophils and/or mast cell-histamine pathway, is important for IgG 1 anaphylaxis. Further analysis of our model in addition to other models will lead to a broader analysis and understanding of the IgG 1 anaphylaxis mechanism.