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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

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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 6

High neutrophil numbers are not responsible for the predominant contribution of neutrophils to ASA.

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High neutrophil numbers are not responsible for the predominant contribu...
(A) WT mice were left untreated (naive, n = 7) or were injected 3 times with BSA in the indicated adjuvant (CFA/IFA, n = 5; alum plus PTX, n = 4; alum, n = 8) or 1 time only with BSA in alum (n = 10). The proportion of granulocytes among wbc and the absolute granulocyte counts in blood 7 days after the last immunization is represented as individual results and mean. PTX, pertussis toxin. (B and C) Absolute granulocyte counts (B) and anti-BSA antibody levels (C) in blood of 5KO mice over time after the last immunization (t = 0) in CFA/IFA (n = 8). (D) Mice from B and C were injected with indicated mAbs and challenged with BSA 7 weeks after the last immunization (n = 4). Statistical significance is indicated. (B–D) Data are represented as mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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