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Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages
06:47

Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages

Published on: May 24, 2019

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Macrophages engulf apoptotic and primary necrotic thymocytes through similar phosphatidylserine-dependent mechanisms

Zsófia Budai1, László Ujlaky-Nagy2, Gréta Nikoletta Kis3

  • 1Department of Biochemistry and Molecular Biology Faculty of Medicine University of Debrecen Hungary.

FEBS Open Bio
|March 15, 2019
PubMed

Insights

Professional phagocytes clear both apoptotic and necrotic cells equally. Key signaling pathways and receptors, like Mer tyrosine kinase and Tim-4, are crucial for this process, suggesting shared clearance mechanisms for different cell death types.

Area of Science:

  • Immunology
  • Cell Biology
  • Pathology

Background:

  • Professional phagocytes are crucial for removing dead cells.
  • Clearance mechanisms for necrotic cells are less understood than for apoptotic cells, despite their importance in pathological conditions.
  • Both apoptotic and necrotic cells require efficient removal to prevent tissue damage and inflammation.

Purpose of the Study:

  • To investigate the phagocytosis of necrotic and apoptotic thymocytes by macrophages.
  • To identify the molecular mechanisms involved in the clearance of necrotic cells.
  • To compare the engulfment processes of apoptotic and necrotic cells.

Main Methods:

  • Utilized mouse bone marrow-derived macrophages (BMDMs) for in vitro phagocytosis assays.
  • Employing heat- or H2O2-killed thymocytes as apoptotic and necrotic cell models.
  • Investigated the role of specific signaling pathways (Mer tyrosine kinase, integrin β3, Ras-related C3 botulinum toxin substrate 1), receptors (Tim-4), and enzymes (transglutaminase 2) in phagocytosis.
  • Examined the effect of nuclear receptor stimulation (liver X, retinoid X, retinoic acid, glucocorticoid) on cell uptake.
  • Conducted electron microscopy to analyze phagosome and phagocytic cup morphology.

Main Results:

  • BMDMs efficiently engulfed both apoptotic and necrotic thymocytes at equal rates, with competition observed when both were present.
  • Phagocytosis of both cell types was reduced by blocking phosphatidylserine, inhibiting Mer tyrosine kinase, Tim-4, integrin β3, or Ras-related C3 botulinum toxin substrate 1 activity, or by using transglutaminase 2-deficient BMDMs.
  • Stimulation of specific nuclear receptors enhanced the uptake of both apoptotic and necrotic cells.
  • Electron microscopy revealed similar phagosome and phagocytic cup morphologies for both apoptotic and necrotic cell engulfment.

Conclusions:

  • Apoptotic and necrotic cells are cleared by macrophages through largely overlapping mechanisms.
  • The same molecular pathways and receptors mediate the uptake of both apoptotic and necrotic cells.
  • Enhancing the uptake of apoptotic cells may also improve the clearance of necrotic cells in vivo, offering therapeutic potential.
Keywords:
apoptosismacrophagesphagocytosisphosphatidylserineprimary necrosis

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