Effect of auranofin, an antirheumatic drug, on neutrophil apoptosis.
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.


CONCLUSIONS
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.
Liu
J
J
Department of Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Akahoshi
T
T
Namai
R
R
Matsui
T
T
Kondo
H
H
D017304:Annexin A5 / Q000032:analysis; D018501:Antirheumatic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001310:Auranofin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000032:analysis; D004587:Electrophoresis, Agar Gel; D006801:Humans; D019041:L-Selectin / Q000032:analysis; D009504:Neutrophils / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D011419:Propidium / Q000032:analysis; D013481:Superoxides / Q000378:metabolism
D017304:Annexin A5; D018501:Antirheumatic Agents; D013481:Superoxides; D019041:L-Selectin; D011419:Propidium; D001310:Auranofin; D004247:DNA