PMID- 22197815 OWN - NLM STAT- MEDLINE DCOM- 20120312 LR - 20120116 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 417 IP - 2 DP - 2012 Jan 13 TI - Both the Fab and Fc domains of IgG are essential for ROS emission from TNF-alpha-primed neutrophils by IVIG. PG - 794-9 LID - 10.1016/j.bbrc.2011.12.038 [doi] AB - 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), 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 FcgammaRIII. These results suggest that binding of IVIG to not only surface antigen(s), but also FcgammaRIII on neutrophils, is involved in IVIG-induced ROS emission from TNF-alpha-primed neutrophils, and contribute to the untoward reactions of IVIG. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Higurashi, Saki AU - Higurashi S AD - Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki 2641, Noda, Chiba 278-8510, Japan. FAU - Machino, Yusuke AU - Machino Y FAU - Suzuki, Emiko AU - Suzuki E FAU - Suzuki, Mami AU - Suzuki M FAU - Kohroki, Junya AU - Kohroki J FAU - Masuho, Yasuhiko AU - Masuho Y LA - eng PT - Journal Article DEP - 20111216 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Immunoglobulin Fab Fragments) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Immunoglobulins, Intravenous) RN - 0 (Reactive Oxygen Species) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Cells, Cultured MH - Humans MH - Immunoglobulin Fab Fragments/*immunology MH - Immunoglobulin Fc Fragments/*immunology MH - Immunoglobulins, Intravenous/*adverse effects/*immunology MH - Neutrophils/*drug effects/immunology MH - Reactive Oxygen Species/metabolism MH - Respiratory Burst/*drug effects/immunology MH - Tumor Necrosis Factor-alpha/immunology EDAT- 2011/12/27 06:00 MHDA- 2012/03/13 06:00 CRDT- 2011/12/27 06:00 PHST- 2011/12/05 00:00 [received] PHST- 2011/12/07 00:00 [accepted] PHST- 2011/12/27 06:00 [entrez] PHST- 2011/12/27 06:00 [pubmed] PHST- 2012/03/13 06:00 [medline] AID - S0006-291X(11)02247-9 [pii] AID - 10.1016/j.bbrc.2011.12.038 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2012 Jan 13;417(2):794-9. doi: 10.1016/j.bbrc.2011.12.038. Epub 2011 Dec 16.