Programmed Necrosis 321 General Considerations

As already stated, the clear morphological and underlying mechanistic distinctions between accidental and programmed necrosis are still lacking (Bredesen 2007). Intuitively, it can be assumed that if the process of cell death is programmed, in the sense of controlled over the time, it can be temporally distinguished from accidental necrosis, which occurs instantly and in a "violent" manner. These theoretical considerations are primordial since they point to the importance of the kinetic analysis of necrotic death phenotypes, which remains the most accurate approach allowing to distinguish between the following outcomes of necrosis (1) primary accidental; (2) primary programmed (controlled) and (3) secondary (which theoretically might occur in both a controlled and uncontrolled manner). However, this does not mean that in extremis [provided that the competent death stimulus is strong enough (Orrenius and Zhivotovsky 2006)], all cell death outcomes should be considered as accidental necrosis and that the study of different death modalities is irrelevant. Indeed, in vivo, the cells are exposed to different death signals of which each can occur in an infinite panel of intensities yielding a great diversity of resulting cell death outcomes. Programmed necrosis might represent one, among a multitude, of end-stage phenotypic expressions.

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