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ECPB 2018, 82(2): 77–85

How Can the Death of Cells Be Useful For a Human Body?


Traditionally, two main types of the cell death (apoptosis and necrosis) are distinguished. The Nomenclature Committee on Cell Death in the last classification of the involved molecular pathways (2018) divided the necrotic and apoptotic morphology of cell death into more than 20 subforms. Besides, earlier it has been also reported about the artificially created cell death pathway.

Apoptosis is a coordinated physiological process of programmed cell death. The cells of the macrophage system should quickly eliminate the dying cells, while producing anti-inflammatory cytokines. During the apoptotic death there is a clear time-dependent sequence of the events initiated by the influence of apoptosis inducer that finally results into the engulf of the apoptotic cell corpses. This is a key sign of the apoptosis that does not cause a damage of the tissue and its inflammation unlike the necrosis.

Necrotic cell death is accompanied by infringement of the plasma membrane integrity and influx of intracellular components into the environment (that causes the inflammation). Recently a new specific type of death has been discovered for neutrophilic granulocytes of blood (neutrophils): Neutrophil Extracellular Traps (NETs). The formation of neutrophil extracellular traps protects the body. Released chromatin immobilizes and neutralizes dangerous and numerically dominant bacteria and help to stop their spreading. NETs can capture another inert material, for example, natural sodium monourate crystals, formed in the case of gout, or artificial nanoparticles, that after contacting with a human body cannot be destroyed or removed (e.g. nanodiamonds or polystyrene nanoparticles). It leads to neutrophils activation and further formation of extracellular neutrophil traps in the place of self-limiting inflammatory process. During some acute inflammatory processes in the internal organs, particularly in the case of acute necrotizing pancreatitis, massive tissue necrosis occurs. Investigation of the internal organs of the patients with the acute inflammation of abdominal cavity allows to examine the interface of the intact and necrotizing tissues and show that necrotizing areas are isolated from the adjacent healthy tissues by aggregated extracellular neutrophil traps.

Aggregated extracellular traps are dense macroscopic structures. It has been found that during excessive infiltration of pancreatic ducts they have been occluded by aggregated extracellular neutrophil traps. At the same time, DNase-1 and DNase-1L3 enzymes-destructors of traps play the important role in protection of vessels from occlusion by neutrophil traps. These two enzymes duplicate each otherfs functions, but when both of them do not function, the blood clots are formed from extracellular neutrophil traps that clog the vessels, and ultimately lead to multiple organ failure and/or death. The smallest capillaries in the lungs are undergo this destructive effect first of all.

Despite the importance of detecting neutrophil extracellular traps, they are often ignored in the routine blood tests, while automated hemoanalyzers do not have appropriate commands to detect them. Modern recommendations underline a problem of ignoring unrecognized objects, including newly formed extracellular traps, in the process of cell counting.

Thus, over the past 15 years, the issue of the extracellular neutrophil traps formation has become extremely important. Current studies convincingly prove the importance of these structures. Extracellular neutrophil traps help not only to stop the spreading of bacteria or to neutralize the objects that are too large for phagocytosis, but they also help to isolate the damaged (necrotic) tissues. At the same time, problems that lead to accumulation of neutrophil traps can trigger multiple organ failure or death.

Article recieved: 25.05.2018

Keywords: neutrophil extracellular traps, inflammation, apoptosis, necrosis

Full text: PDF (Ukr) 644K

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