Using a model of active systemic anaphylaxis (ASA) — which is induced by immunizing mice with an antigen plus adjuvant and then administering the antigen intravenously — Jönsson et al. found that anaphylaxis still developed in mast cell-deficient mice and in 5KO mice (which lack all IgE and IgG receptors except for the activating IgG2 receptor FcγRIV). Interestingly, 5KO mice treated with FcγRIV-specific blocking antibodies were protected from ASA, indicating that an anaphylactic reaction can be triggered via FcγRIV activation alone. FcγRIV is expressed by macrophages and neutrophils, but not by cells traditionally linked with anaphylaxis, such as basophils and mast cells. In keeping with this, whole body luminescence experiments suggested that neutrophils are systemically activated within minutes of ASA induction. Furthermore, although depletion of neutrophils protected 5KO mice from anaphylaxis, depletion of monocytes and macrophages did not affect ASA development.
A distinct model of shock — passive systemic anaphylaxis (PSA) — is induced by pre-injecting mice with antigen-specific IgE or IgG antibodies before delivering the antigen intravenously. Strikingly, the authors found that neutrophil depletion protected wild-type mice from anaphylaxis in a model of PSA induced by polyclonal IgG antibodies, whereas mice lacking both basophils and mast cells were still susceptible to anaphylaxis. Thus, neutrophils not only contribute to the development of IgG-induced PSA, but are in fact essential for the anaphylactic reaction in this setting.
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