How Macrophages Deal With Death

Nat Rev Immunol. 2019 Sep;19(9):539-549. doi: 10.1038/s41577-019-0167-y.

Abstract

Tissue macrophages rapidly recognize and engulf apoptotic cells. These events require the display of so-called eat-me signals on the apoptotic cell surface, the most fundamental of which is phosphatidylserine (PtdSer). Externalization of this phospholipid is catalysed by scramblase enzymes, several of which are activated by caspase cleavage. PtdSer is detected both by macrophage receptors that bind to this phospholipid directly and by receptors that bind to a soluble bridging protein that is independently bound to PtdSer. Prominent among the latter receptors are the MER and AXL receptor tyrosine kinases. Eat-me signals also trigger macrophages to engulf virus-infected or metabolically traumatized, but still living, cells, and this 'murder by phagocytosis' may be a common phenomenon. Finally, the localized presentation of PtdSer and other eat-me signals on delimited cell surface domains may enable the phagocytic pruning of these 'locally dead' domains by macrophages, most notably by microglia of the central nervous system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, Surface / physiology
  • Apoptosis*
  • Humans
  • Macrophages / physiology*
  • Membrane Proteins / physiology
  • Milk Proteins
  • Phagocytosis
  • Phosphatidylserines / physiology
  • Receptor Protein-Tyrosine Kinases / physiology
  • c-Mer Tyrosine Kinase / physiology

Substances

  • Antigens, Surface
  • MFGE8 protein, human
  • Membrane Proteins
  • Milk Proteins
  • Phosphatidylserines
  • TIMD4 protein, human
  • MERTK protein, human
  • Receptor Protein-Tyrosine Kinases
  • TYRO3 protein, human
  • c-Mer Tyrosine Kinase