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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

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Phagocytosis and clearance of apoptotic cells is mediated by MER

R S Scott1, E J McMahon, S M Pop

  • 1UNC Neuroscience Center, USA.

Nature
|May 11, 2001
PubMed

Insights

The Mer receptor tyrosine kinase is crucial for macrophages to clear apoptotic cells, preventing inflammation and autoimmune responses. This discovery impacts understanding of diseases like lupus.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Apoptosis, or programmed cell death, is vital for tissue homeostasis and immune system function.
  • Efficient clearance of apoptotic cells by macrophages prevents inflammation and autoimmunity.
  • The Axl/Mer/Tyro3 receptor tyrosine kinase family plays a role in cellular signaling.

Purpose of the Study:

  • To investigate the role of the Mer receptor tyrosine kinase in the clearance of apoptotic cells.
  • To determine if Mer deficiency affects macrophage phagocytic function.
  • To explore the implications of impaired apoptotic cell clearance in autoimmune diseases.

Main Methods:

  • Utilized mer(kd) mice with a truncated Mer protein to assess macrophage function.
  • Generated chimaeric mice by reconstituting with wild-type bone marrow.
  • Isolated primary macrophages for phagocytosis assays, testing clearance of apoptotic thymocytes and other particles.
  • Analyzed autoantibody levels in mer(kd) mice.

Main Results:

  • Macrophages from mer(kd) mice exhibited a deficiency in clearing apoptotic thymocytes.
  • This phagocytic defect was specific to apoptotic cells and not related to Fc receptor-mediated phagocytosis or other particle ingestion.
  • Reconstitution with wild-type bone marrow corrected the clearance defect in chimaeric mice.
  • mer(kd) mice showed increased levels of nuclear autoantibodies.

Conclusions:

  • The Mer receptor tyrosine kinase is essential for the efficient engulfment and clearance of apoptotic cells.
  • Impaired Mer function can lead to the accumulation of apoptotic cells and may contribute to autoimmune responses.
  • This finding has significant implications for understanding and potentially treating inflammatory and autoimmune diseases, including systemic lupus erythematosus.

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