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Rapid, noninflammatory and PS-dependent phagocytic clearance of necrotic cells

U A Hirt1, M Leist

  • 1Faculty of Biology, University of Konstanz, X911, D-78457 Konstanz, Germany.

Cell Death and Differentiation
|September 23, 2003
PubMed

Insights

This study reveals that necrotic cells, unlike heat-killed cells, are efficiently cleared by phagocytes. Surface phosphatidylserine on these necrotic cells is crucial for their uptake by macrophages and microglia.

Area of Science:

  • Cell Biology
  • Immunology
  • Pathology

Background:

  • Understanding non-apoptotic cell death pathways is crucial in pathological conditions.
  • Information regarding the clearance and function of non-apoptotic cell corpses is limited.

Purpose of the Study:

  • To model and compare two distinct cell death modes: apoptosis and programmed cell death with necrotic morphology (necPCD).
  • To investigate the phagocytosis of these cell corpses by macrophages and microglia.
  • To identify the molecular mechanisms underlying the uptake of necrotic cells.

Main Methods:

  • Induction of apoptosis and necPCD in human Jurkat T cells.
  • Co-culture of cell corpses with primary macrophages and microglia.
  • Assessment of cytokine release (TNF) from phagocytes.
  • Development of a novel assay to detect surface phosphatidylserine.
  • Investigation of calcium signaling's role in phosphatidylserine translocation.

Main Results:

  • Both apoptotic and necPCD cells reduced TNF release from macrophages, unlike heat-killed cells.
  • Macrophages and microglia efficiently engulfed necPCD cells.
  • Macrophages preferentially phagocytosed necPCD cells over apoptotic cells when offered together.
  • Phosphatidylserine translocation to the surface of necPCD cells was observed, independent of calcium signals.
  • Surface phosphatidylserine was essential for the phagocytosis of necrotic cells by macrophages and microglia.

Conclusions:

  • Necrotic cell death pathways generate phagocytosis-competent corpses.
  • Surface phosphatidylserine acts as a key 'eat-me' signal for the clearance of necrotic cells by myeloid phagocytes.
  • This study provides insights into the clearance mechanisms of non-apoptotic cell death, relevant to inflammatory and autoimmune diseases.

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