Mouse and human neutrophils induce anaphylaxis

Institut Pasteur, Unité d'Allergologie Moléculaire et Cellulaire, Département d'Immunologie, Paris, France.
The Journal of clinical investigation (Impact Factor: 13.22). 03/2011; 121(4):1484-96. DOI: 10.1172/JCI45232
Source: PubMed


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.

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    • "PAF also causes severe hypotension and cardiovascular dysfunction during acute anaphylaxis, an effect that, at least in mice, is dependent on a PAF-mediated activation of eNOS and consequent NO formation (Cauwels et al., 2006). In mouse models, PAF antagonists effectively attenuated IgG-induced anaphylaxis (Jiao et al., 2014; Jonsson et al., 2011; Strait et al., 2002; Tsujimura et al., 2008) and peanut-induced anaphylaxis severity (Arias et al., 2009), but did not effectively attenuate IgEmediated anaphylaxis, which is more dependent on histamine release (Strait et al., 2002). In humans, it has not been clearly established whether anaphylaxis is mediated through a classical IgE-mediated pathway, an alternative IgG-mediated pathway or both (Finkelman, 2007). "
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    • "Those results suggest that neutrophils are responsible for the FcγRIV-mediated component of active systemic anaphylaxis in mice and that this component is sufficient to trigger a full-blown anaphylaxis response. Additional experiments indicated that the neutrophil-dependent anaphylactic reaction was mediated primarily by PAF rather than histamine (Jönsson et al., 2011). Importantly, active systemic anaphylaxis could be restored by adoptive transfer of human neutrophils to FcRγ−/− animals (Jönsson et al., 2011) or by transgenic expression of human FcγRIIA in FcRγ−/− mice (Jönsson et al., 2012), suggesting that human neutrophils may also be able to mediate systemic anaphylactic reactions. "
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