Phagocytosis of Apoptotic Cells

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.

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.

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.

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.

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.

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.

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.