IMMUNOBIOLOGY Human FcRIIA induces anaphylactic and allergic reactions

IgE and IgE receptors (FcRI) are well-known inducers of allergy. We recently found in mice that active systemic ana-phylaxis depends on IgG and IgG recep-tors (FcRIIIA and FcRIV) expressed by neutrophils, rather than on IgE and FcRI expressed by mast cells and basophils. In humans, neutrophils, mast cells, baso-phils, and eosinophils do not express FcRIIIA or FcRIV, but FcRIIA. We there-fore investigated the possible role of FcRIIA in allergy by generating novel FcRIIA-transgenic mice, in which vari-ous models of allergic reactions induced by IgG could be studied. In mice, FcRIIA was sufficient to trigger active and pas-sive anaphylaxis, and airway inflamma-tion in vivo. Blocking FcRIIA in vivo abolished these reactions. We identified mast cells to be responsible for FcRIIA-dependent passive cutaneous anaphy-laxis, and monocytes/macrophages and neutrophils to be responsible for FcRIIA-dependent passive systemic anaphy-laxis. Supporting these findings, human mast cells, monocytes and neutrophils produced anaphylactogenic mediators af-ter FcRIIA engagement. IgG and FcRIIA may therefore contribute to allergic and anaphylactic reactions in humans. (Blood. 2012;119(11):2533-2544