Biochemical and Biophysical Research Communications, Vol.417, No.2, 794-799, 2012
Both the Fab and Fc domains of IgG are essential for ROS emission from TNF-alpha-primed neutrophils by IVIG
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-alpha priming of the cells. The ROS emission from TNF-alpha-primed neutrophils occurred by activation with whole gammaglobulin (GG) molecules, but not F(ab')(2), Fe, 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 Fc gamma RIII. These results suggest that binding of IVIG to not only surface antigen(s), but also Fc gamma RIII on neutrophils, is involved in IVIG-induced ROS emission from TNF-a-primed neutrophils, and contribute to the untoward reactions of IVIG. (C) 2011 Elsevier Inc. All rights reserved.