Human FcγRIIA induces anaphylactic and allergic reactions.

Abstract:

:IgE and IgE receptors (FcεRI) are well-known inducers of allergy. We recently found in mice that active systemic anaphylaxis depends on IgG and IgG receptors (FcγRIIIA and FcγRIV) expressed by neutrophils, rather than on IgE and FcεRI expressed by mast cells and basophils. In humans, neutrophils, mast cells, basophils, and eosinophils do not express FcγRIIIA or FcγRIV, but FcγRIIA. We therefore investigated the possible role of FcγRIIA in allergy by generating novel FcγRIIA-transgenic mice, in which various models of allergic reactions induced by IgG could be studied. In mice, FcγRIIA was sufficient to trigger active and passive anaphylaxis, and airway inflammation in vivo. Blocking FcγRIIA in vivo abolished these reactions. We identified mast cells to be responsible for FcγRIIA-dependent passive cutaneous anaphylaxis, and monocytes/macrophages and neutrophils to be responsible for FcγRIIA-dependent passive systemic anaphylaxis. Supporting these findings, human mast cells, monocytes and neutrophils produced anaphylactogenic mediators after FcγRIIA engagement. IgG and FcγRIIA may therefore contribute to allergic and anaphylactic reactions in humans.

journal_name

Blood

journal_title

Blood

authors

Jönsson F,Mancardi DA,Zhao W,Kita Y,Iannascoli B,Khun H,van Rooijen N,Shimizu T,Schwartz LB,Daëron M,Bruhns P

doi

10.1182/blood-2011-07-367334

subject

Has Abstract

pub_date

2012-03-15 00:00:00

pages

2533-44

issue

11

eissn

0006-4971

issn

1528-0020

pii

blood-2011-07-367334

journal_volume

119

pub_type

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