| Autor: |
Yamashita, Kouhei, Takahashi, Atsushi, Kobayashi, Susumu, Hirata, Hirokazu, Mesner, Peter W., Kaufmann, Scott H., Yonehara, Shin, Yamamoto, Kokichi, Uchiyama, Takashi, Sasada, Masataka |
| Zdroj: |
Blood; January 1999, Vol. 93 Issue: 2 p674-685, 12p |
| Abstrakt: |
Tumor necrosis factor-? (TNF-?) exerts two separate effects on neutrophils, stimulating effector functions while simultaneously inducing apoptosis. We examined here the involvement of caspases in neutrophil apoptosis and the effect of TNF-?–induced apoptosis on reactive oxygen production. Immunoblotting and affinity labeling showed activation of caspase-8, caspase-3, and a caspase with a large subunit of 18 kD (T18) in TNF-?–treated neutrophils. Active caspase-6 and -7 were not detectable in this cell type. Caspase-8 activated caspase-3 and T18 in neutrophil cytoplasmic extracts. zVAD-fmk blocked neutrophil apoptosis, in parallel with the inhibition of caspase activation. TNF-?–induced caspase activation was accompanied by a decrease in the ability of neutrophils to release superoxide anion. Conversely, TNF-? treatment in the presence of zVAD-fmk caused a prolonged augmentation of superoxide release. Granulocyte-macrophage colony-stimulating factor inhibited TNF-?–induced caspase activation and apoptosis, while reversing the diminution in superoxide release. These observations not only suggest that a caspase cascade mediates apoptotic events and downregulates oxygen radical production in TNF-?–treated neutrophils, but also raise the possibility that suppression of caspase activation with enhanced proinflammatory actions of TNF-? may underlie the pathogenesis of inflammatory diseases. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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