37.6
Phagocytosis of Apoptotic Cells
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocyt…
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.
View the full transcript and gain access to JoVE Core videos
Q1: Why do phagocytes need to remove apoptotic cells quickly?
Apoptotic cells leak their contents, which can trigger local inflammation if not rapidly removed. Phagocytes like macrophages engulf apoptotic cells and release anti-inflammatory cytokines such as IL-10 and TGF-β, preventing damage to neighboring cells and avoiding autoimmune diseases and necrosis.
Q2: What role does phosphatidylserine play in phagocytosis of apoptotic cells?
In normal cells, flippase maintains phosphatidylserine in the inner plasma membrane leaflet. During apoptosis, executioner caspases inactivate flippase, and scramblase transports phosphatidylserine to the outer leaflet where it acts as an eat-me signal recognized by phagocyte receptors.
Q3: How do phagocytes locate and recognize apoptotic cells?
Apoptotic cells release find-me signals like lysophosphatidylcholine and ATP that attract phagocytes. Once phagocytes arrive, they recognize eat-me signals including phosphatidylserine and apoptotic cell-associated molecular patterns. Bridging proteins also bind exposed phosphatidylserine, facilitating indirect receptor recognition.
Q4: What happens to apoptotic cells after phagocytes engulf them?
The engulfed apoptotic body becomes a phagosome, which fuses with a lysosome to form a phagolysosome. Lysosomal enzymes break down ingested materials into nucleotides, amino acids, and sterols that are recycled by the cell.
Q5: What is the difference between professional and non-professional phagocytes?
Professional phagocytes like macrophages and immature dendritic cells efficiently engulf apoptotic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also participate in phagocytosis but are less effective at removing apoptotic bodies and preventing inflammation.
Q6: How do normal cells avoid being phagocytosed?
Normal cells express protective markers like CD47 receptors and CD31 that prevent phagocyte recognition and attachment. During apoptosis, CD31 expression is lost, allowing phagocytes to recognize and engulf the dying cell through exposed eat-me signals.
Q7: How does phagocytosis of apoptotic cells relate to the broader cell death process?
Phagocytosis is the critical final stage of apoptosis, where professional phagocytes remove dying cells to maintain tissue homeostasis. This process prevents the inflammatory consequences that would occur if apoptotic cells were not cleared, distinguishing it from other forms of cell death like necrosis.