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Review
. 2000 Apr;53(2):55-63.
doi: 10.1136/mp.53.2.55.

Apoptosis

S Afford  1 , S Randhawa
Affiliations
Review

Apoptosis

S Afford et al. Mol Pathol. 2000 Apr.

Abstract

Apoptosis is the genetically regulated form of cell death that permits the safe disposal of cells at the point in time when they have fulfilled their intended biological function. Examples of apoptosis can be cited throughout the whole of the animal and plant kingdoms. It is a vitally important process during normal development and the adult life of many living organisms. In humans, dysregulation of apoptosis can result in inflammatory, malignant, autoimmune, and neurodegenerative diseases. In addition, infectious agents, including viruses, exploit cellular apoptosis in the host to evade the immune system. This review gives a brief historical perspective of some of the landmark discoveries in apoptosis research. The morphological and biochemical stages of apoptosis are then covered, followed by an overview of how it can be studied in the laboratory. Finally, the implications for therapeutic intervention in disease treatment are discussed.

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Figures

Figure 1
Figure 1
The stages of apoptosis. This diagram illustrates the four basic stages of the apoptotic pathway. Once the cell has reached stage two and the caspase pathway has been activated it is believed that the process is irreversible and the cell cannot be rescued. After stage three, if the cell is in close enough proximity to a phagocytic neighbour and is displaying the right molecular signature it is engulfed and broken down within the phagocyte. If the apoptotic cell is not recognised it will eventually assume necrotic morphology, so called “secondary necrosis”.
Figure 2
Figure 2
Apoptotic cell death mediated by the Fas receptor pathway. Effector cells (for example, activated T lymphocytes) present the Fas ligand (FasL) in a conformation that permits crosslinking and aggregation of the Fas receptor on the target cell. The clustering of Fas is the first step in activating the intracellular apoptotic cascade. Formation of a complex, the Fas associated death domain (FADD), then results in binding and activation of procaspase 8 and the caspase cascade.
Figure 3
Figure 3
The morphology of apoptosis. This photomicrograph shows a culture of promonocytic U937 cells, some of which show classic morphological features of apoptosis (arrow A). The cell marked N shows the normal morphology of a viable neighbour for comparison.
Figure 4
Figure 4
Phagocytic recognition of an apoptotic cell. At present, little is known about the interactions between apoptotic cells and phagocytes, but a series of molecules seem to be important including phosphatidylserine (PS), anionic phospholipids, and intracellular adhesion molecule 3 (ICAM 3). The hierarchical nature of these interactions is not yet known but recent evidence suggests that ICAM 3 partners CD14 on the macrophage. An important pairing also seems to be between PS and the vitronectin receptor or CD36. This probably occurs via thrombospondin, which can avidly bind both molecules on the phagocyte.
Figure 5
Figure 5
Electrophoretic analysis of DNA from apoptotic cells. DNA extracts can be purified, run on an agarose gel, and stained with fluorescent ethidium bromide. DNA from apoptotic cells (aged blood polymorphs in this case) forms a distinctive laddering pattern as a result of endonuclease cleavage (lane 1). Lane 2, DNA isolated from necrotic cells; lanes and 6, no sample; lanes 3 and 4, DNA immediately after isolation (before treatment); lane 7, standard DNA molecular weight markers. Band sizes are in kDa.
Figure 6
Figure 6
Identification of apoptotic cells in tissue sections using in situ DNA end labelling (ISEL). This figure shows a section of human liver tissue from a patient with end stage primary biliary cirrhosis. Strongly staining ISEL positive cells (red) can be seen; in this case, in the bile duct within the portal tract.
Figure 7
Figure 7
Quantitative assessment of apoptosis using flow cytometry. This figure shows a typical profile for activated peripheral blood lymphocytes that have been stained with propidium iodide (PI) or annexin V and subjected to fluorescence activated cell sorting. Each dot represents an individual cell. Viable cells stain with neither PI nor annexin V. Apoptotic cells stain with annexin V only, whereas necrotic cells stain with both.
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