Efferocytosis

In cell biology, efferocytosis (from efferre, Latin for 'to take to the grave', 'to bury') is the process by which dying/dead cells (e.g. apoptotic or necrotic) are removed by phagocytic cells. It can be regarded as the 'burying of dead cells'.[1]

During efferocytosis, the cell membrane of phagocytic cells engulfs the apoptotic cell, forming a large fluid-filled vesicle containing the dead cell. This ingested vesicle is called an efferosome (in analogy to the term phagosome). This process is similar to macropinocytosis.

For apoptosis, the effect of efferocytosis is that dead cells are removed before their membrane integrity is breached and their contents leak into the surrounding tissue. This prevents exposure of tissue to toxic enzymes, oxidants and other intracellular components such as proteases and caspases.[2]

Efferocytosis can be performed not only by 'professional' phagocytic cells such as macrophages or dendritic cells, but also by many other cell types including epithelial cells and fibroblasts. To distinguish them from living cells, apoptotic cells carry specific 'eat me' signals, such as the presence of phosphatidyl serine (resulting from phospholipid flip-flop) or calreticulin on the outer leaflet of the cell membrane.[3]

Efferocytosis triggers specific downstream intracellular signal transduction pathways, for example resulting in anti-inflammatory, anti-protease and growth-promoting effects. Conversely, impaired efferocytosis has been linked to autoimmune disease and tissue damage. Efferocytosis results in production by the ingesting cell of mediators such as hepatocyte- and vascular endothelial growth factor, which are thought to promote replacement of the dead cells.[2]

Defective efferocytosis has been demonstrated in such diseases as cystic fibrosis and bronchiectasis, COPD, asthma and idiopathic pulmonary fibrosis, rheumatoid arthritis, systemic lupus erythematosus, glomerulonephritis and atherosclerosis.[2]

Footnotes

  1. ↑ deCathelineau AM, Henson PM (2003). "The final step in programmed cell death: phagocytes carry apoptotic cells to the grave". Essays Biochem. 39: 105–17. PMID 14585077.
  2. ↑ 2.0 2.1 2.2 Vandivier RW, Henson PM, Douglas IS (June 2006). "Burying the dead: the impact of failed apoptotic cell removal (efferocytosis) on chronic inflammatory lung disease". Chest 129 (6): 1673–82. doi:10.1378/chest.129.6.1673. PMID 16778289.
  3. ↑ Gardai SJ, McPhillips KA, Frasch SC et al. (October 2005). "Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte". Cell 123 (2): 321–34. doi:10.1016/j.cell.2005.08.032. PMID 16239148.