Mouse and human neutrophils induce anaphylaxis.

Area of Science:

• Immunology
• Allergy Research

Background:

• Anaphylaxis is a severe hypersensitivity reaction typically involving IgE antibodies, mast cells, and histamine.
• Alternative anaphylaxis pathways involving IgG antibodies and basophils have been observed.
• Previous models indicated mast cells and basophils were not essential for active systemic anaphylaxis.

Purpose of the Study:

• To identify the specific antibodies, receptors, and cells involved in active systemic anaphylaxis in mouse models.
• To elucidate the mechanisms underlying IgG-mediated anaphylaxis.

Main Methods:

• Investigated the roles of various antibodies, receptors (FcγRIIIA, FcγRIV), and cells (neutrophils, basophils) in active systemic anaphylaxis.
• Monitored neutrophil activation in vivo during anaphylactic reactions.
• Utilized neutrophil depletion and reconstitution experiments in mice.

Main Results:

• Identified involvement of IgG antibodies, FcγRIIIA, FcγRIV, platelet-activating factor, neutrophils, and basophils in active systemic anaphylaxis.
• Demonstrated that neutrophils are sufficient to induce anaphylaxis in mice.
• Showed that neutrophil depletion inhibited both active and passive systemic anaphylaxis.

Conclusions:

• Neutrophils, IgG antibodies, and their receptors are key mediators of active systemic anaphylaxis in mice.
• Neutrophils may contribute to anaphylaxis in humans, presenting potential therapeutic targets.
• Findings challenge traditional IgE-centric views of anaphylaxis and highlight novel mechanisms.