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UvA-DARE ( Digital Academic Repository ) Neutrophil cell death : mechanisms and regulation
| Content Provider | Semantic Scholar |
|---|---|
| Author | Maianski, Nikolai A. Roos, Dirk Kuijpers, Taco W. |
| Copyright Year | 2009 |
| Abstract | Neutrophil apoptosis constitutes a way of managing neutrophil-mediated reactions. It allows coping with infections but avoiding overt bystander tissue damage. Using digitonin-based subcellular fractionation and Western blotting, we found that spontaneous apoptosis of human neutrophils (after -20 h of culture) was associated with translocation of two proapoptotic Bcl2 homologues Bid and Bax to the mitochondria and truncation of Bid, with subsequent release of Omi/HtrA2 and Smac/DIABLO into the cytosol. These events were accompanied by processing and increased enzymatic activity of caspase-8, -9, and -3. Granulocyte-colony stimulating factor (G-CSF)-mediated reduction in apoptosis coincided with inhibition of all these reactions. The G-CSF-induced effects were differentially dependent on newly synthesised mediators. Whereas inhibition of Bax targeting to the mitochondria and inhibition of caspase activation by G-CSF were dependent on protein synthesis, Bid truncation and redistribution were prevented by G-CSF irrespective of the presence of the protein synthesis inhibitor cycloheximide. Apparently, the observed Bid changes were dispensable for neutrophil apoptosis. Although the regulators of the inhibitor of apoptosis proteins (IAPs) Omi/HtrA2 and Smac/DIABLO were released into the cytosol during apoptosis, we did not observe cleavage of X-linked LAP, which suggests that another mechanism of LAP deactivation is involved. Together, our results support an integrative role of the mitochondria in induction and/or amplification of caspase activity and disclose that G-CSF may act by blocking Bid/Bax redistribution and inhibiting caspase activation. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://pure.uva.nl/ws/files/3396705/43503_UBA002001397_09.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |