Mouse and human neutrophils induce anaphylaxis
Friederike Jönsson, … , Marc Daëron, Pierre Bruhns
Friederike Jönsson, … , Marc Daëron, Pierre Bruhns
Published March 23, 2011
Citation Information: J Clin Invest. 2011;121(4):1484-1496. https://doi.org/10.1172/JCI45232.
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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 8

Human neutrophils restore anaphylaxis in resistant mice.

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Human neutrophils restore anaphylaxis in resistant mice. (A) Representat...
(A) Representative histogram plots of human FcR expression on purified human neutrophils. (B) Histograms show the binding of indicated IgG IC or anti-FLAG mAbs (FLAG) to indicated FLAG-tagged FcγR+ CHO transfectants. Both polymorphic variants of human FcγRIIA at position 131 are used and represented. All human FcγRIIIB variants (NA1, NA2, and SH) gave identical results; only variant NA1 is represented. (C) Expression of CD62L on purified human neutrophils from healthy donors incubated with GPI/anti-GPI IC (n = 5) and controls. Data represent individual results and means. (D) FcRγ–/– mice were immunized with BSA, injected or not with 2 × 106 human neutrophils, challenged with BSA, and central temperatures monitored (n = 3). Data are represented as mean ± SEM. Statistical differences are indicated. (E and F) Purified human neutrophils originating from 1 healthy donor were divided equally in 2 fractions. One fraction was injected into a naive (open symbols) and 1 fraction into a BSA-immunized FcRγ–/– mice (closed symbols) at (E) 7.5 × 105 neutrophils per mouse (n = 3) or (F) 1.5 × 106 neutrophils per mouse (n = 2). Mice were subsequently challenged with BSA and central temperatures were monitored. Each symbol corresponds to the pair of mice that received neutrophils from 1 specific donor. *P < 0.05; **P < 0.01; ***P < 0.001.