Phagoptosis (cell death by phagocytosis) is a type of cell death caused by the cell being phagocytosed (i.e. eaten) by another cell, and therefore this form of cell death is prevented by blocking phagocytosis. Phagocytosis of an otherwise-viable cell may occur because the cell is recognised as stressed, activated, senescent, damaged, pathogenic or non-self, or is misrecognised. Cells are phagocytosed as a result of: i) expressing "eat-me" signals on their surface, ii) losing "don’t-eat-me" signals, and/or iii) binding of opsonins. It is clear that otherwise-viable cells can expose/bind such phagocytosis-promoting signals as a result of cell stress, activation or senescence. Phagoptosis is probably the most common form of cell death in the body as it is responsible for erythrocyte turnover. And there is increasing evidence that it mediates physiological death of neutrophils, T cells, platelets and stem cells, and thereby regulates inflammation, immunity, clotting and neurogenesis. Phagoptosis is a major form of host defence against pathogens and cancer cells. However, recent evidence indicates that excessive phagoptosis may kill host cells in inflammatory conditions, contributing to haemophagic conditions, and neuronal loss in the inflamed brain.
Mechanism Phagoptosis is normally caused by: the cell exposing on its surface so-called "eat-me" signals, and/or the cell no longer exposing "don't-eat-me" signals and/or the cell being opsonised i.e. binding soluble proteins that tag the cell for phagocytosis. For example, phosphatidylserine is an "eat-me" signal that, when exposed on the surface of a cell, triggers phagocytes (i.e. cells that eat other cells) to eat that cell. Phosphatidylserine is normally found on the inside of healthy cells, but can become exposed on the surface of dying, activated or stressed cells. Phagocytosis of such cells requires specific receptors on the phagocyte that recognise either phosphatidylserine directly or opsonins bound to the phosphatidylserine or other "eat-me" signals, such as calreticulin. "Don't-eat-me" signals include CD47, which when expressed on the surface of a cell, inhibit phagocytosis of that cell, by activating SIRP-alpha receptors on the phagocyte. Opsonins are normally soluble proteins, which when bound to the surface of a cell induce phagocytes to phagocytose that cell. Opsonins include Mfge8, Gas6, Protein S, antibodies and complement factors C1q and C3b.
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