What is Apoptosis?
In 1972, three pathologists observed cell death in pathological tissues and coined the term "apoptosis" to distinguish the concept of physiological cell death from the concept of passive cell death, necrosis [1].
Apoptosis is a process of programmed cell death that occurs in multicellular organisms. It is a highly regulated and controlled process that occurs normally during development and aging as a homeostatic mechanism to maintain cell populations in tissues [2].
During early development, apoptosis is used to eliminate unwanted cells; for example, those between the fingers of a developing hand. In adults, apoptosis is used to rid the body of cells that have been damaged beyond repair. Apoptosis also plays a role in preventing cancer. If apoptosis is prevented for some reason, it can lead to uncontrolled cell division and subsequent development of tumors.
Morphology of Apoptosis
Morphological changes during apoptosis include cell shrinkage and pyknosis visible under light microscopy during the early process of apoptosis. Pyknosis is the result of chromatin condensation, and this is the most characteristic feature of apoptosis. Extensive plasma membrane blebbing occurs followed by karyorrhexis and separation of cell fragments into apoptotic bodies during a process called "budding". These bodies are subsequently phagocytosed by macrophages, parenchymal cells, or neoplastic cells and degraded within phagolysosomes.
Fig.1 The Process of Apoptosis
Mechanisms of Apoptosis
The two main pathways of apoptosis are extrinsic and intrinsic as well as the perforin/granzyme pathway. Each requires specific triggering signals to begin an energy-dependent cascade of molecular events. Each pathway activates its initiator caspase (8, 9, 10) which in turn activates the executioner caspase-3. However, granzyme work in a caspase-independent fashion. The execution pathway results in characteristic cytomorphological features including cell shrinkage, chromatin condensation, formation of cytoplasmic blebs and apoptotic bodies, and finally phagocytosis of the apoptotic bodies by adjacent parenchymal cells, neoplastic cells or macrophages[2, 3].
Fig.2 Schematic Representation of Apoptotic
Confusing Points: Apoptosis and Necrocytosis
Although the results of apoptosis and necrosis are similar, their processes and manifestations are quite different. Apoptosis is referred to as "programmed" cell death because it happens due to biochemical instructions in the cell's DNA; this is opposed to the process of "necrosis" when a cell dies due to outside trauma or deprivation.
Table 1. Comparison of morphological features of apoptosis and necrosis
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Apoptosis
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Necrosis
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Single cells or small clusters of cells
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Often contiguous cells
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Cell shrinkage and convolution
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Cell swelling
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Pyknosis and karyorrhexis
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Karyolysis, pyknosis, and karyorrhexis
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Intact cell membrane
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Disrupted cell membrane
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Cytoplasm retained in apoptotic bodies
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Cytoplasm released
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No inflammation
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Inflammation usually present
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References
[1] Kaczanowski, Szymon. Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging[J]. Physical Biology, 2016, 13(3): 031001.
[2] Elmore, S., Apoptosis: a review of programmed cell death. Toxicol Pathol, 2007. 35(4): 495-516.
[3] Susin, S.A., et al., Two distinct pathways leading to nuclear apoptosis. J Exp Med, 2000. 192(4): 571-80.
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