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 3

Neutrophils and FcγRIV account for IgG2b-IC induced PSA in WT mice, and neutrophils account for GPI/anti-GPI–PSA in WT mice.

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Neutrophils and FcγRIV account for IgG2b-IC induced PSA in WT mice, and ...
(A, B, and D) Indicated mice were injected with preformed IgG2b-IC (monoclonal IgG2b anti-DNP mAb plus DNP-HSA), and central temperatures were monitored (A, n = 4; B, n = 3; D, n = 3). (C) 5KO mice were preinjected or not with anti-FcγRIV Abs before challenge with IgG2b-IC. Plasma was collected 20 minutes after challenge, and PAF concentration was determined. Means of triplicates are represented. (E–I) Mice were injected with indicated mAbs or isotype controls before injection of preformed polyclonal IgG-IC (GPI/anti-GPI). Central temperatures were monitored (E, n = 4; F, n = 4; G, n = 5; H, n = 4; I, n = 4). (G) Statistical differences between the untreated and the anti-Gr1–treated groups are indicated for each time point if significant. (A–I) Data are represented as mean ± SEM. (A, B, and D–I) Data are representative of 2 independent experiments. Note that no mortality was observed in all these experiments. *P < 0.05; **P < 0.01; ***P < 0.001.