Neutrophils give us a shock

Abstract

Systemic anaphylaxis is generally recognized as a severe allergic reaction caused by IgE-mediated activation of mast cells, leading to massive release of vasoactive mediators that induce acute hypotension and shock. However, experimental evidence in mice suggests that this view is too simple. Using a variety of techniques to manipulate immune cell makeup, Jönsson et al. come to the conclusion in this issue of the JCI that recognition of IgG1 and IgG2 antibodies by FcγRIII and FcγRIV receptors on neutrophils is a major pathway for induction of anaphylaxis. These exciting results suggest that we have to reevaluate our models for anaphylaxis in humans, which will have a direct impact on our therapeutic approaches for prevention of this potential deadly hypersensitivity reaction.

Figure 1. Mast cells, basophils, and neutrophils in anaphylaxis.

Following allergen exposure, IgE and IgG Abs are produced. IgE binds to FcεRs on mast cells, priming the cells for a secondary response. Following second exposure, the allergen binds to IgE on mast cell receptors, activating histamine release. Allergens also form immune complexes with IgG1- and IgG2-activating basophils and neutrophils through FcγRIII and FcγRIV, respectively, leading to PAF release. Neutrophils also express FcγRIII, and they also respond to IgG1/allergen complexes.