Mouse and human neutrophils induce anaphylaxis
Friederike Jönsson, David A. Mancardi, Yoshihiro Kita, Hajime Karasuyama, Bruno Iannascoli, Nico Van Rooijen, Takao Shimizu, Marc Daëron, Pierre Bruhns
Friederike Jönsson, David A. Mancardi, Yoshihiro Kita, Hajime Karasuyama, Bruno Iannascoli, Nico Van Rooijen, Takao Shimizu, Marc Daëron, Pierre Bruhns
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Research Article

Mouse and human neutrophils induce anaphylaxis

Abstract

Anaphylaxis is a life-threatening hyperacute immediate hypersensitivity reaction. Classically, it depends on IgE, FcεRI, mast cells, and histamine. However, anaphylaxis can also be induced by IgG antibodies, and an IgG1-induced passive type of systemic anaphylaxis has been reported to depend on basophils. In addition, it was found that neither mast cells nor basophils were required in mouse models of active systemic anaphylaxis. Therefore, we investigated what antibodies, receptors, and cells are involved in active systemic anaphylaxis in mice. We found that IgG antibodies, FcγRIIIA and FcγRIV, platelet-activating factor, neutrophils, and, to a lesser extent, basophils were involved. Neutrophil activation could be monitored in vivo during anaphylaxis. Neutrophil depletion inhibited active, and also passive, systemic anaphylaxis. Importantly, mouse and human neutrophils each restored anaphylaxis in anaphylaxis-resistant mice, demonstrating that neutrophils are sufficient to induce anaphylaxis in mice and suggesting that neutrophils can contribute to anaphylaxis in humans. Our results therefore reveal an unexpected role for IgG, IgG receptors, and neutrophils in anaphylaxis in mice. These molecules and cells could be potential new targets for the development of anaphylaxis therapeutics if the same mechanism is responsible for anaphylaxis in humans.

Authors

Friederike Jönsson, David A. Mancardi, Yoshihiro Kita, Hajime Karasuyama, Bruno Iannascoli, Nico Van Rooijen, Takao Shimizu, Marc Daëron, Pierre Bruhns

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Figure 2

Neutrophil transfer restores ASA, and neutrophils are immediately and systemically activated during ASA.

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Neutrophil transfer restores ASA, and neutrophils are immediately and sy...
(A) BSA-immunized FcRγ–/– mice were injected i.v. with neutrophils from FcRγ–/– mice (n = 4) or from 5KO mice (n = 5), challenged with BSA, and central temperatures measured. Statistical differences are indicated for each time point if significant. Note that no mortality was observed during this experiment. (B) Purified bone marrow neutrophils from 5KO or FcRγ–/– mice were stimulated with antigen alone (Ag) or with IgG IC, or preincubated with anti-FcγRIV Abs before stimulation with IC (IC plus anti-FcγRIV), and PAF concentration was determined in culture supernatants. Means of triplicates are represented. (C) Naive or BSA-immunized 5KO mice were anesthetized, challenged with BSA (t = 0), and injected with luminol (t = 5 minutes). Representative images show color-coded maps of photon flux superimposed on black and white photographs of mice (15- to 20-minute time frame after challenge) (n = 2). (D) Time course of photon fluxes from naive and BSA-immunized 5KO mice (n = 3) following BSA challenge (t = 0). (A and D) Data are represented as mean ± SEM. (C and D) Data are representative from 2 independent experiments. *P < 0.05; **P < 0.01; ***P < 0.001.