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Annexin A5 inhibits engulfment through internalization of PS-expressing cell membrane patches

Heidi Kenis1, Hugo van Genderen, Niko M Deckers

  • 1Department of Biochemistry, Cardiovascular Research Institute Maastricht, PO Box 616, 6200 MD Maastricht, The Netherlands.

Experimental Cell Research
|December 29, 2005
PubMed

Insights

Phosphatidylserine (PS) is a key "eat me" signal on apoptotic cells. Annexin A5 binding during apoptosis significantly inhibits phagocytosis, suggesting other signals cooperate with PS for efficient cell clearance.

Area of Science:

  • Cell Biology
  • Immunology
  • Biochemistry

Background:

  • Apoptosis and efficient clearance of apoptotic cells are crucial for preventing disease.
  • Phosphatidylserine (PS) is the best-characterized
  • eat me
  • signal on apoptotic cells.
  • Annexin A5 binds PS and has been shown to mediate internalization of PS-expressing membrane patches.

Purpose of the Study:

  • To investigate the role of phosphatidylserine (PS) in the phagocytosis of apoptotic cells using annexin A5.
  • To determine how annexin A5 affects the phagocytic clearance of apoptotic cells expressing PS.

Main Methods:

  • Utilized a novel flow cytometry-based phagocytosis assay.
  • Administered annexin A5 to apoptotic cells at different stages (post-apoptosis vs. during apoptosis).
  • Compared the inhibitory effects of annexin A5 with a mutant (M23) and annexin A1.

Main Results:

  • Annexin A5 addition inhibited phagocytosis by 20% when added to cells after apoptosis completion.
  • Inhibition increased to over 50% when annexin A5 was added during the apoptotic process.
  • Internalized annexin A5 did not prevent surface PS expression, and annexin A1 did not enhance inhibition.

Conclusions:

  • Annexin A5 binding during apoptosis significantly impairs phagocytic clearance of PS-expressing cells.
  • The results suggest that other ligands within the PS-expressing membrane patch, in addition to PS itself, function as "eat me" signals.
  • This highlights a complex interplay of signals in the efficient removal of apoptotic cells.

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