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 4

FcγRIIIA and FcγRIV account for ASA in WT mice.

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FcγRIIIA and FcγRIV account for ASA in WT mice. (A) Representative densi...
(A) Representative density plots of CD11b and FcγRIIIA expression on blood leukocytes from WT or FcγRIIIA–/– mice. (B) FcγRIIB–/– mice or FcγRIIB/IIIA–/– double-deficient mice were injected with anti-FcγRIIIA mAb or not before injection with IgG1-IC (n = 3). Central temperatures were monitored. Statistical differences between groups treated with 0 and 25 μg and those treated with 0 and 50 μg are indicated under and over the horizontal axis, respectively, for each time point if significant. (C–E) Indicated mice were immunized and challenged with BSA. Central temperatures and survival rates were monitored. (C) ASA in WT mice injected with anti-FcγRIIIA (n = 5) or vehicle (n = 3) before BSA challenge. (D) ASA in WT mice injected with vehicle (n = 8), anti-FcγRIIIA mAbs (n = 7), anti-FcγRIV mAbs (n = 8), or both mAbs (n = 7). Statistical differences between the vehicle-treated group and each experimental group are indicated at the right end of each curve. (E) ASA in WT mice injected with indicated mAbs before BSA challenge (n = 4). (A–E) Data are represented as mean ± SEM and are representative of 2 independent experiments. *P < 0.05; **P < 0.01; ***P < 0.001. X’s represent 100% mortality in the vehicle group.