Anaphylaxis: Lessons from mouse models

• Published in: Journal of allergy and clinical immunology Vol. 120; no. 3; pp. 506 - 515
• Main Author: Finkelman, Fred D.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.09.2007; Elsevier; Elsevier Limited
• Subjects: Allergies; Allergy; Allergy and Immunology; anaphylaxis; Anaphylaxis - immunology; Anaphylaxis - physiopathology; Animals; Biological and medical sciences; Disease Models, Animal; FcγRIIb; FcγRIII; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Human subjects; Humans; IgE; IgG; IL-13; IL-4; Immunoglobulin E - immunology; Immunoglobulin G - immunology; Immunopathology; Laboratory animals; Ligands; Medical sciences; Mice - immunology; mouse; nitric oxide; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Signal Transduction - immunology; Species Specificity; Allergy; PECAM-1; nitric oxide; MMCP1; FcγRIII; IgE; IgG; IL-4; anaphylaxis; IL-13; MAFA; FcγRIIb; ITIM; PCA; mouse; STAT; PAF; ITAM; gp49B1; PIR; SHIP; SHP; OVA; TRPM4; Glycoprotein 49B1; Signal transducer and activator of transcription; Platelet-activating factor; Paired immunoglobulin-like receptor; Platelet/endothelial cell adhesion molecule-1; Mast cell function–associated antigen; Src homology 2–containing tyrosine phosphatase; Transient receptor potential cation channel, subfamily M, member 4; Chicken ovalbumin; Src homology 2–containing inositol phosphatase; Intracellular immunoreceptor tyrosine-based inhibition motif; Intracellular immunoreceptor tyrosine-based activation motifs; Mouse mast cell protease 1; Passive cutaneous anaphylaxis; Animal model; FcγRII receptor; Immunoglobulin receptor; FcγIIB receptor; Interleukin 4; Anaphylaxis; Immunology; Immunopathology; Immunoglobulins; Cytokine; Rodentia; Interleukin 13; Vertebrata; Mammalia; Mouse; Animal; Nitric oxide; FcγRIII receptor
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2007.07.033

Studies with mouse models demonstrate 2 pathways of systemic anaphylaxis: a classic pathway mediated by IgE, FcɛRI, mast cells, histamine, and platelet-activating factor (PAF) and an alternative pathway mediated by IgG, FcγRIII, macrophages, and PAF. The former pathway requires much less antigen and antibody than the latter. This is modified, however, by IgG antibodies that prevent IgE-mediated anaphylaxis by intercepting antigen before it binds to mast cell–associated IgE. Consequently, IgG antibodies block systemic anaphylaxis induced by small quantities of antigen but mediate systemic anaphylaxis induced by larger quantities. The importance of the alternative pathway in human subjects is unknown, but human IgG, IgG receptors, macrophages, mediators, and mediator receptors have appropriate properties to support this pathway if sufficient IgG and antigen are present. The severity of systemic anaphylaxis is increased by nitric oxide produced by the enzyme endothelial nitric oxide synthase and by the cytokines IL-4 and IL-13 and decreased by endogenous β-adrenergic stimulation and receptors that contain ITIM that bind tyrosine phosphatases. Anaphylaxis is also suppressed by other receptors and ion channels that function through distinct mechanisms. Unlike systemic anaphylaxis, intestinal anaphylaxis (allergic diarrhea) is almost totally IgE and mast cell dependent and is mediated predominantly by PAF and serotonin. Some potent food allergens, including peanuts and tree nuts, can directly enhance anaphylaxis by stimulating an anaphylactoid response through the innate immune system. Results of these studies suggest novel prophylactic agents, including nonstimulatory anti-IgE mAbs, IL-4 receptor antagonists, PAF antagonists, and agents that cross-link FcɛRI or FcγRIII to an ITIM–containing inhibitory receptor.