Molecular mechanisms of anaphylaxis: Lessons from studies with murine models

• Published in: Journal of Allergy and Clinical Immunology Vol. 115; no. 3; pp. 449 - 457
• Main Authors: Finkelman, Fred D., Rothenberg, Marc E., Brandt, Eric B., Morris, Suzanne C., Strait, Richard T.
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01.03.2005; Elsevier Limited
• Subjects: Allergies; Anaphylaxis - immunology; Animals; Blocking antibody; Disease Models, Animal; FcγRIIb; FcγRIII; FcεRI; Food allergies; Histamine; Humans; IgE; IL-4 receptor α chain; Immunization; Immunoglobulin E - immunology; Immunoglobulin G - immunology; Mice - immunology; Permeability; Rodents; Serotonin; Signal Transduction - immunology; Studies; IL-4 receptor α chain; PAF; FcγRIII; IgE; TNP; FcεRI; Blocking antibody; OVA; FcγRIIb; IL-4Rα
• ISSN: 0091-6749; 1097-6825; 1365-2567
• DOI: 10.1016/j.jaci.2004.12.1125

Studies with murine models demonstrate 2 pathways of systemic anaphylaxis: one mediated by IgE, FcεRI, mast cells, histamine, and platelet-activating factor (PAF), and the other mediated by IgG, FcγRIII, macrophages, and PAF. The former pathway requires much less antibody and antigen than the latter. As a result, IgG antibody can block IgE-mediated anaphylaxis induced by small quantities of antigen without mediating FcγRIII-dependent anaphylaxis. The IgE pathway is most likely responsible for most human anaphylaxis, which generally involves small amounts of antibody and antigen; similarities in the murine and human immune systems suggest that the IgG pathway might mediate disease in persons repeatedly exposed to large quantities of antigen. Mice, like human subjects, can experience IgE/FcεRI/mast cell–mediated gastrointestinal and systemic anaphylaxis in response to ingested antigen. Gastrointestinal symptoms depend on serotonin and PAF; mediator dependence of systemic symptoms has not been determined. Both local and systemic anaphylaxis induced by ingested antigens might be blocked by IgA and IgG antibodies. IL-4 and IL-13 signaling through the IL-4 receptor α chain, in addition to promoting the mastocytosis and IgE antibody production that mediate most human anaphylaxis, exacerbates the effector phase of anaphylaxis by increasing target cell responsiveness to vasoactive mediators. As a result, IL-4 receptor α chain antagonists might be particularly effective suppressors of anaphylaxis.