Neutrophils give us a shock

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. I turned to Wikipedia when I was searching for a way to explain the basics of anaphylaxis and came across the following statement: “True anaphylaxis is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE).” This is the classic teaching, present in all the immunology textbooks, but the paper in this issue of the JCI by Jönsson et al. (1) informs us that this view is, at best, incomplete. Instead, we learn that anaphylaxis can be mediated by neutrophils recognizing IgG/antigen complexes. In addition to turning around our understanding of anaphylaxis, this paper adds to the growing list of neutrophil functions besides just bacterial killing and protease production (2). Lately we have learned that neutrophils are major sources of cytokines and chemokines (3, 4). They play a direct role in influencing the recruitment and activation of monocytes/macrophages, T cells, and NK cells during inflammation (5–7). Neutrophils have been implicated as the primary initiators of immune complex–mediated diseases (8, 9). And now the shocking news (pun intended!) that they are major players in initiating anaphylaxis.