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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

Requirement for Rho GTPases and PI 3-kinases during apoptotic cell phagocytosis by macrophages

Y Leverrier1, A J Ridley

  • 1Ludwig Institute for Cancer Research, 91 Riding House Street, W1P 8BT, and the Department of Biochemistry and Molecular Biology, University College London, WC1E 6BT, London, United Kingdom.

Current Biology : CB
|March 7, 2001
PubMed

Insights

Macrophages engulf apoptotic cells using lamellipodia and an actin cup. Rho GTPases (Rac1, Cdc42) are essential, while PI 3-kinases play a distinct role in this crucial process for tissue repair.

Area of Science:

  • Cell Biology
  • Immunology
  • Biochemistry

Background:

  • Apoptotic cell clearance by phagocytes is vital for tissue remodeling and resolving inflammation.
  • Mechanisms triggering apoptotic cell engulfment by mammalian phagocytes remain largely undescribed.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which macrophages engulf apoptotic cells.
  • To investigate the roles of Rho GTPases and PI 3-kinases in apoptotic cell phagocytosis.

Main Methods:

  • Utilized primary murine bone marrow-derived macrophages.
  • Employed Clostridium difficile toxin B to inhibit Rho GTPases.
  • Used PI 3-kinase inhibitor LY294002.
  • Observed lamellipodia extension, actin cup formation, and phosphotyrosine accumulation.

Main Results:

  • Macrophages extend lamellipodia to engulf apoptotic cells, forming an actin cup with accumulated phosphotyrosine.
  • Inhibition of Rho GTPases prevented phagocytosis and F-actin/phosphotyrosine accumulation.
  • Specific Rho GTPases Rac1 and Cdc42 are required for uptake, while Rho inhibition enhances it.
  • PI 3-kinase inhibition blocked phagocytosis but not F-actin/phosphotyrosine accumulation.

Conclusions:

  • Both Rho GTPases and PI 3-kinases are involved in apoptotic cell phagocytosis.
  • These signaling pathways play distinct roles in the engulfment process.
  • Findings provide insight into the molecular regulation of efferocytosis.

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