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- W2592687454 abstract "The mechanism of neutrophil cell death is an important factor in the proper resolution of inflammation. Neutrophils have been shown to undergo delayed apoptosis under hypoxic conditions such as those that are prevalent at sites of inflammation, but the eventual fate of the cells is unknown. We found that whereas phosphatidylserine exposure and morphology changes associated with apoptosis were not seen, caspase 3, which is a hallmark of apoptosis, was activated under hypoxic conditions. Time lapse microscopy confirmed it was activated in all neutrophils. Electron microscopy images showed clear morphological changes in hypoxic neutrophils. Several lines of evidence support the induction of autophagy: hypoxia inducible factor-1α (HIF-1α) was stabilised; there was increased expression of BNIP3, a downstream gene of HIF-1 that regulates autophagy; electron microscopy images showed autophagosome formation; Western blotting and immunofluorescence demonstrated an increase in the phosphatidylethanolamine-conjugated form of Microtubule-associated protein 1A/1B-light chain 3 (LC3 II), a marker of autophagy. We also investigated the effect of transient hypoxia on stimulated neutrophils. There was minimal superoxide production when oxygen was limiting, and this is likely to be due to a reduction in oxygen supply for the NADPH oxidase. When the cells were returned to a normoxic environment, superoxide production was measurable and it was apparent that extended hypoxic incubation did not result in increased functional capacity with respect to oxidant production. Also no difference was observed in bacterial killing capacity after exposure to hypoxia Therefore, our results suggest that although neutrophils survive for longer periods in a hypoxic environment an increase in functional capacity is not observed." @default.
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- W2592687454 date "2016-11-01" @default.
- W2592687454 modified "2023-09-27" @default.
- W2592687454 title "Inhibition of Neutrophil Apoptosis and Initiation of an Autophagy-Like Process in Hypoxia and Effects on Neutrophil Function" @default.
- W2592687454 doi "https://doi.org/10.1016/j.freeradbiomed.2016.10.166" @default.
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