Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal

Cell. 2003 Jun 13;113(6):717-30. doi: 10.1016/s0092-8674(03)00422-7.

Abstract

Efficient engulfment of the intact cell corpse is a critical end point of apoptosis, required to prevent secondary necrosis and inflammation. The presentation of "eat-me" signals on the dying cell is an important part of this process of recognition and engulfment by professional phagocytes. Here, we present evidence that apoptotic cells secrete chemotactic factor(s) that stimulate the attraction of monocytic cells and primary macrophages. The activation of caspase-3 in the apoptotic cell was found to be required for the release of this chemotactic factor(s). The putative chemoattractant was identified as the phospholipid, lysophosphatidylcholine. Further analysis showed that lysophosphatidylcholine was released from apoptotic cells due to the caspase-3 mediated activation of the calcium-independent phospholipase A(2). These data suggest that in addition to eat-me signals, apoptotic cells display attraction signals to ensure the efficient removal of apoptotic cells and prevent postapoptotic necrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ankyrin Repeat / genetics
  • Apoptosis / physiology*
  • COS Cells
  • Caspase 3
  • Caspases / metabolism*
  • Cell Surface Extensions / metabolism
  • Chemotaxis / physiology*
  • Enzyme Inhibitors / pharmacology
  • Eukaryotic Cells / enzymology*
  • Eukaryotic Cells / metabolism
  • HT29 Cells
  • Humans
  • Inflammation / enzymology
  • Lipid Metabolism
  • Lysophosphatidylcholines / metabolism*
  • Mice
  • Phagocytes / enzymology*
  • Phagocytes / metabolism
  • Phagocytosis / physiology*
  • Phospholipases A / metabolism
  • Protein Synthesis Inhibitors / pharmacology
  • Signal Transduction / physiology

Substances

  • Enzyme Inhibitors
  • Lysophosphatidylcholines
  • Protein Synthesis Inhibitors
  • Phospholipases A
  • CASP3 protein, human
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases