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Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages
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Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages

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Mer receptor tyrosine kinase mediates both tethering and phagocytosis of apoptotic cells

I Dransfield1, A Zagórska2, E D Lew2

  • 1MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.

Cell Death & Disease
|February 20, 2015
PubMed

Insights

The Mer receptor tyrosine kinase (RTK) and its ligands rapidly bind and clear apoptotic cells (ACs). Mer uniquely tethers ACs to macrophages, driving their engulfment and aiding inflammatory response resolution.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Apoptotic cells are cleared daily by macrophages to resolve inflammation.
  • Receptor tyrosine kinase (RTK) Mer plays a role in phagocytosis.
  • Phosphatidylserine (PtdSer) on apoptotic cells signals for clearance.

Purpose of the Study:

  • Investigate the role of RTK Mer, Protein S, and Gas6 in apoptotic cell recognition and capture.
  • Elucidate the binding kinetics and mechanisms of Mer-mediated phagocytosis.
  • Determine if Mer-mediated phagocytosis requires αV integrins.

Main Methods:

  • Studied Mer receptor tyrosine kinase (RTK) and its ligands, Protein S and Gas6.
  • Investigated binding kinetics to phosphatidylserine (PtdSer)-displaying apoptotic cells (ACs).
  • Assessed macrophage phagocytosis of ACs opsonized with Mer ligands, with and without αV integrins.

Main Results:

  • Mer ligands exhibited rapid binding kinetics to PtdSer-displaying ACs.
  • ACs were co-opsonized by multiple PtdSer opsonins.
  • Mer-mediated phagocytosis occurred independently of αV integrins.
  • Mer demonstrated a novel role in tethering ACs to macrophages.
  • Mer-mediated tethering and engulfment were distinguished by kinase activity requirements.

Conclusions:

  • Mer is uniquely capable of both tethering ACs to macrophages and driving their internalization.
  • Mer-mediated phagocytosis is a key mechanism for resolving inflammatory responses.
  • The Mer pathway offers a potential target for modulating immune responses.

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