37.6:
Phagocytosis of Apoptotic Cells
The contents of an apoptotic cell can leak out and if not quickly removed, lead to local inflammation. Phagocytes, such as macrophages, prevent inflammation by engulfing apoptotic cells and releasing anti-inflammatory cytokines.
In normal cells, flippase maintains phosphatidylserine in the inner leaflet of the plasma membrane.
During apoptosis, executioner caspases inactivate flippase, and scramblase transports phosphatidylserine to the outer leaflet, where it acts as an eat-me signal for phagocytes.
Apoptotic cells also secrete bridging proteins that bind to the exposed phosphatidylserine and other chemical signals that attract phagocytes.
Receptors on phagocytes bind directly to the phosphatidylserine or indirectly through the bridging proteins. The attachment leads to the internalization of the apoptotic bodies by the phagocytes.
The engulfed apoptotic body is now called a phagosome, which will then fuse with a lysosome to form a phagolysosome. Lysosomal enzymes then break down the ingested materials.
37.6:
Phagocytosis of Apoptotic Cells
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes. For example, red blood cells display CD47 receptors that block phagocytosis. Another marker, CD31, also known as platelet endothelial cell adhesion molecule-1, is expressed by normal cells, which prevents phagocyte attachment. During apoptosis, CD31 is not expressed, leading to phagocyte recognition and phagocytosis.
Apoptotic cells release 'find-me' signals such as lysophosphatidylcholine, sphingosine-1-phosphate, fractalkine, thrombospondin-1, ATP, and UTP to help phagocyte recognition. Once the phagocytes reach the location, the apoptotic cells display 'eat-me' signals, such as apoptotic cell-associated molecular patterns (ACAMP) and phosphatidylserine. When phagocytes attach to apoptotic cells, they release anti-inflammatory cytokines such as IL-10 and TGF-ꞵ, creating a non-inflammatory microenvironment. This prevents damage to neighboring cells. Once the apoptotic cells are internalized, they are broken down into nucleotides, amino acids, and sterols which are further recycled.