title: Both the Fab and Fc domains of IgG are essential for ROS emission from TNF-α-primed neutrophils by IVIG.
abstract: Intravenous immunoglobulin (IVIG) is currently a very important therapeutic used for not only infectious diseases, but also for autoimmune diseases such as idiopathic thrombocytopenic purpura (ITP). Untoward reactions of IVIG have been thought to result from complement activation by aggregated IgG in IVIG. In addition, the aggregates have been known to activate neutrophils, which may result in the untoward reactions. However, the effect and mechanism of IVIG on neutrophils remain unclear. In this study, we investigated the activation of neutrophils by IVIG in terms of their reactive oxygen species (ROS) emission to elucidate the mechanisms. IVIG-induced ROS emission from purified neutrophils was remarkably augmented by TNF-α priming of the cells. The ROS emission from TNF-α-primed neutrophils occurred by activation with whole gammaglobulin (GG) molecules, but not F(ab')(2), Fc, or a mixture of F(ab')(2) and Fc. ROS emission by GG was inhibited by the F(ab')(2) fragment and an inhibitory antibody against FcγRIII. These results suggest that binding of IVIG to not only surface antigen(s), but also FcγRIII on neutrophils, is involved in IVIG-induced ROS emission from TNF-α-primed neutrophils, and contribute to the untoward reactions of IVIG.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki 2641, Noda, Chiba 278-8510, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Higurashi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Machino
authors.forename: Emiko
authors.initials: E
authors.lastname: Suzuki
authors.forename: Mami
authors.initials: M
authors.lastname: Suzuki
authors.forename: Junya
authors.initials: J
authors.lastname: Kohroki
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Masuho
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects* / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D016756:Immunoglobulins, Intravenous; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha