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Paris, March 24, 2011

Anaphylactic shock: the key players identified

Researchers from the Institut Pasteur and Inserm (French National Institute for Health and Medical Research) have recently identified, in animals, the otherwise unexpected culprits responsible for anaphylactic shock. If confirmed in upcoming clinical investigations, these results could markedly improve means to handle this potentially fatal medical emergency.


An anaphylactic shock is a hyper-acute systemic allergic reaction. It can generate a cardiovascular failure, leading to death within minutes. It can be induced by numerous substances. Drugs are among the most common causes, followed by food, more and more frequently, and by insect venoms. It can also occur during surgery in patients sensitive to latex or anesthetics.

Until now, anaphylaxis was thought to be due to the release of pro-inflammatory mediators, essentially histamine, by very rare cells, mast cells in tissues and basophils in blood, when activated by antibodies produced in extremely small amounts, IgE antibodies.

By using an experimental model that mimics drug-induced anaphylaxis seen in humans, researchers from the Institut Pasteur and Inserm have discovered that lgG, the most abundant antibody found in plasma, and polynuclear neutrophils, the most common white blood cell found in the blood stream, are major contributors to this reaction.

Pierre Bruhns and Marc Daëron of the Molecular and Cellular Allergology Unit (Institut Pasteur – Inserm U.760) and their colleagues have shown that neutrophil activation by lgG antibodies is both necessary and sufficient for inducing anaphylaxis. Neutrophils from normal mice, or even human neutrophils, could indeed restore anaphylactic shocks in mice genetically resistant to anaphylaxis. Reciprocally, neutrophil depletion prevented anaphylaxis and associated death in normal mice.

Researchers have also shown that the main mediator responsible for anaphylactic symptoms is Platelet-Activating Factor (PAF). PAF antagonists, but not antihistamines, indeed prevented death. Supporting the clinical significance of these experimental results, circulating PAF was reported to be correlated with the severity of anaphylactic shocks in humans.

If confirmed in humans, these results could therefore open new therapeutic approaches of anaphylaxis.

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Picture: Inflammatory neutrophils (nuclei in blue). © F.Jönsson/Institut Pasteur

Source

Mouse and Human Neutrophils induce Anaphylaxis, The Journal of Clinical Investigation, published online on March 23, 2011.

Friederike Jönsson* (1,2), David A. Mancardi* (1,2), Yoshihiro Kita (3), Hajime Karasuyama (4,5), Bruno Iannascoli (1,2), Nico Van Rooijen (6), Takao Shimizu (3), Marc Daëron** (1,2) and Pierre Bruhns** (1,2)

* contributed equally to this study **senior co-authors

(1) Institut Pasteur, Immunology Department, Molecular and Cellular Allergology Unit, Paris, France.
(2) INSERM, U.760, Paris, France.
(3) Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
(4) Department of Immune Regulation,
(5) JST, CREST, Tokyo Medical and Dental University Graduate School, Yushima, Bunkyo-ku, Tokyo, Japan.
(6) Department of Molecular Cell Biology, VU Medical Center, Amsterdam, The Netherlands.

Contacts

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