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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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The C4b-binding protein-protein S complex inhibits the phagocytosis of apoptotic cells

Lena Kask1, Leendert A Trouw, Björn Dahlbäck

  • 1Lund University, The Wallenberg Laboratory, Department of Clinical Chemistry, University Hospital Malmö; S-205 02 Malmö, Sweden.

The Journal of Biological Chemistry
|April 21, 2004
PubMed

Insights

C4b-binding protein (C4BP) bound to protein S (PS) inhibits the clearance of apoptotic cells by macrophages. However, this complex may prevent secondary necrosis by inhibiting complement attack.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Phagocytosis of apoptotic cells is crucial for tissue homeostasis.
  • C4b-binding protein (C4BP) is a major inhibitor of complement pathways.
  • Protein S (PS) binds to C4BP and has a high affinity for phosphatidylserine on apoptotic cells.

Purpose of the Study:

  • To investigate the role of the C4BP-PS complex in the phagocytosis of apoptotic cells.
  • To determine how C4BP-PS affects the interaction between apoptotic cells and macrophages.

Main Methods:

  • Experiments using primary human macrophages and THP-1 cells.
  • Utilizing serum depleted of PS and adding purified C4BP-PS complex.
  • Employing monoclonal antibodies against the Gla domain of PS to block interactions.

Main Results:

  • Free PS enhances the engulfment of apoptotic cells by macrophages.
  • The C4BP-PS complex significantly inhibits this phagocytosis.
  • The inhibitory effect of C4BP-PS can be blocked by antibodies targeting PS.

Conclusions:

  • While free PS promotes apoptotic cell clearance, the C4BP-PS complex hinders it.
  • The C4BP-PS complex may offer a protective role by preventing secondary necrosis through complement inhibition.

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