J Liu1, T Akahoshi, R Namai, T Matsui, H Kondo. 1. Department of Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Abstract
OBJECTIVE: The effects of auranofin (AF) on apoptosis and on the biological functions of neutrophils were investigated. METHODS: Neutrophils were incubated with various concentrations of AF for different periods. Cell viability was determined by the MTS assay and apoptosis was evaluated by flow cytometric analysis of propidium iodide (PI)- staining of the nuclei and annexin-V staining of phosphatidylserine in the cell membrane. The effect of AF on the expression of adhesion molecules (CD62L and CD11b/CD18) and on the generation of O2- by neutrophils was also determined. RESULTS: At a low concentration (1 microM), AF significantly prolonged neutrophil survival by delaying spontaneous apoptosis. Neutrophils incubated with AF for 12 and 24 hours maintained the capacity to express adhesion molecules and generate O2-. In contrast, a higher AF concentration (5 microM) shortened neutrophil survival by the induction of cell necrosis. CONCLUSION: Although the biological significance of inhibitory effect of AF on neutrophil apoptosis remains unclear, it seems to be unlikely that AF exerts the anti-inflammatory effect in vivo by directly suppressing neutrophil functions. Since AF has a wide range of effects on leukocytes, its therapeutic benefit in rheumatoid arthritis may be mediated in a complex manner.
OBJECTIVE: The effects of auranofin (AF) on apoptosis and on the biological functions of neutrophils were investigated. METHODS: Neutrophils were incubated with various concentrations of AF for different periods. Cell viability was determined by the MTS assay and apoptosis was evaluated by flow cytometric analysis of propidium iodide (PI)- staining of the nuclei and annexin-V staining of phosphatidylserine in the cell membrane. The effect of AF on the expression of adhesion molecules (CD62L and CD11b/CD18) and on the generation of O2- by neutrophils was also determined. RESULTS: At a low concentration (1 microM), AF significantly prolonged neutrophil survival by delaying spontaneous apoptosis. Neutrophils incubated with AF for 12 and 24 hours maintained the capacity to express adhesion molecules and generate O2-. In contrast, a higher AF concentration (5 microM) shortened neutrophil survival by the induction of cell necrosis. CONCLUSION: Although the biological significance of inhibitory effect of AF on neutrophil apoptosis remains unclear, it seems to be unlikely that AF exerts the anti-inflammatory effect in vivo by directly suppressing neutrophil functions. Since AF has a wide range of effects on leukocytes, its therapeutic benefit in rheumatoid arthritis may be mediated in a complex manner.
Authors: Melissa A Fath; Iman M Ahmad; Carmen J Smith; Jacquelyn Spence; Douglas R Spitz Journal: Clin Cancer Res Date: 2011-08-15 Impact factor: 12.531