Intravenous immunoglobulin preparations promote apoptosis in lipopolysaccharide-stimulated neutrophils via an oxygen-dependent pathway in vitro.
Since prolonged survival of activated neutrophils has an autotoxic potential, neutrophil apoptosis plays an important role in the rapid resolution of inflammation. Intravenous immunoglobulin (IVIG) preparations, which are beneficial therapeutic agents for the treatment of autoimmune diseases and systemic inflammatory diseases, have been reported to induce apoptosis of lymphocytes and endothelial cells in vitro. In the present study, we investigated whether IVIG may induce apoptosis of neutrophils cultured in vitro. After neutrophils prestimulated with or without lipopolysaccharide (LPS) were cultured in the presence or absence of IVIG, the number of apoptotic cells, intracellular H2O2 and GSH were measured by a flow cytometer. IVIG induced apoptosis of LPS-stimulated neutrophils dose dependently, but not in unstimulated neutrophils. Although anti-Fas monoclonal antibodies (mAbs) had no effect on the IVIG-induced apoptosis in the LPS-stimulated neutrophils, anti-Fc gamma receptor (Fc gammaR) II- and III-blocking mAbs significantly inhibited the IVIG-induced apoptosis. IVIG increased the production of intracellular H2O2, while it decreased the production of GSH, in the LPS-stimulated neutrophils. Furthermore, a specific NADPH oxidase inhibitor and anti-oxidants inhibited the IVIG-induced neutrophil apoptosis. Therefore, these findings indicate that IVIG preparations induce apoptosis of LPS-stimulated neutrophils and suggest that the IVIG-induced apoptosis may be mediated by an oxygen-dependent pathway via Fc gammaRII and III.
Takeshita
Seiichiro
S
Ibaraki University, Faculty of Education, Ibaraki, Japan. takeshit@mx.ibaraki.ac.jp
Tsujimoto
Hiroshi
H
Nakatani
Keigo
K
D017209:Apoptosis; D002478:Cells, Cultured; D005978:Glutathione / Q000096:biosynthesis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
D016756:Immunoglobulins, Intravenous; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D005978:Glutathione