Dear colleagues, I cannot find a comprehensive answer on the question: how does, if at all, necrosis actually kill cells surrounding necrotic are? Is the necrotic spread caused by an extracellular damaged caused by the necrotic fluid? Or is it just a spreading initiation of the necrotic cell death taking place inside the cells adjacent to the necrotic area due to internal causes (e.g. energy deprivation)?
Over the last three decades, apoptotic cell death has been well characterized at both the genetic and biochemical levels. These studies have demonstrated that while apoptosis is often initiated in response to toxic insults, the ultimate fate of the injured cell is self-determined. During apoptosis, the injured cell degrades its internal constituents and signals for the clearance of the resulting corpse through phagocytosis. While apoptotic cell death has become increasingly well defined, our notions of necrotic cell death has become progressively more vague. At present, the most widely accepted way to define necrotic cell death is to show that the death was not mediated by apoptosis. The concept that necrosis is unprogrammed is reinforced by the fact that necrotic cell death can be caused by exposures of cells to supraphysiological conditions such as mechanical force, heat, or cold. Even in response to a certain dose of death-inducing agent, features of both apoptosis and necrosis may coexist in the same cell. In addition, if not engulfed by neighboring cells or in cell culture, where phagocytosis does not usually happen, dead cells in the late stages of apoptosis may present necrotic features due to the loss of cellular energy and plasma membrane integrity. This process is called “apoptotic necrosis” or “secondary necrosis". While mediators of necrosis such as calcium and reactive oxygen species (ROS) have been reported to contribute to apoptosis, recent studies have begun to demonstrate that the ability of such mediators to initiate necrotic cell death depends on active participation by the dying cell. The core events of necrosis are bioenergetic failure and rapid loss of plasma membrane integrity. These can result from defined molecular events that occur in the dying cell, including increased mitochondrial ROS production, channel-mediated calcium uptake, activation of nonapoptotic proteases, and/or enzymatic destruction of cofactors required for ATP production.
While Blessy's detailed description explains most of the points, I would add some more to specifically answer your question. The necrotic fluid might contribute to adjacent cell death in vivo as there are necrotic zones reported in the literature.
Dear Blessy and Goodwin, thank you for your valuable responses!
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