Study on the molecular mechanism of the lack of the oligonucleosomal DNA fragmentation in the non-apoptotic, non-necrotic neutrophil death induced by ONO-AE-248

Objective To investigate the molecular mechanism of the lack of the oligonucleosomal DNA fragmentation in the neutrophil death induced by ONO-AE-248. Methods Human neutrophils were cultured in the presence or absence of ONO-AE-248 for the indicated time periods. TUNEL and confocal microscopy were used to detect apoptosis. Caspase-3 activation was examined by western blot analysis. Expression levels of DNA fragmation factor 40 (DFF40) were detected by RT-PCR. Results ONO-AE-248-induced neutro-phil death was negative in TUNEL assay. Western blot showed that ONO-AE-248 did not affect pro-caspase-3 degradation. RT-PCR showed that ONO-AE-248 caused the down-regulation of DFF40 expression. Conclu-sion The experimental data suggested that the way of DNA fragmentation in the ONO-AE-248-induced neu-trophil death is different from apoptosis. The down-regulation of DFF40 expression is likely to be one of ex-planations for the lack of the oligonueleosomal DNA fragmentation in the neutrophil death. Key words: ONO-AE-248;  Neutropbils;  Non-apoptosis;  DNA fragmation;  DFF40