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Updated: Jul 5, 2026

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

Complete downmodulation of P-selectin glycoprotein ligand in monocytes undergoing apoptosis

Jan-Julius Stampfuss1, Petra Censarek, Jens W Fischer

  • 1Institut für Pharmakologie, Universität Duisburg-Essen, Universitätsklinikum Essen, Hufelandstr. 55, D-45122 Essen, Germany.

Arteriosclerosis, Thrombosis, and Vascular Biology
|May 3, 2008
PubMed
Abstract

Insights

Apoptotic monocytes shed P-selectin glycoprotein ligand-1 (PSGL-1), reducing cell interactions and thrombogenicity. This shedding is mediated by an ADAM metalloproteinase, suggesting a mechanism to control inflammation and clotting.

Area of Science:

  • Cell Biology
  • Immunology
  • Hematology

Background:

  • Apoptotic monocytes release microparticles implicated in thrombosis via P-selectin glycoprotein ligand-1 (PSGL-1).
  • Understanding PSGL-1 regulation in apoptosis is crucial for its role in thrombogenicity.

Purpose of the Study:

  • To systematically investigate the regulation of PSGL-1 expression and function in apoptotic monocytic cells.
  • To identify the mechanism and enzyme responsible for PSGL-1 downmodulation during monocyte apoptosis.

Main Methods:

  • Flow cytometry, immunofluorescence microscopy, and immunoblotting to assess PSGL-1 expression.
  • Platelet-leukocyte and leukocyte-endothelial cell interaction assays.
  • Protease inhibitor screening, knock-out, and siRNA experiments to identify the cleaving enzyme.

Main Results:

  • PSGL-1 expression was significantly reduced in apoptotic monocytes due to proteolytic shedding.
  • This shedding led to a complete loss of PSGL-1-mediated platelet-leukocyte and leukocyte-endothelial cell interactions.
  • An ADAM metalloproteinase, inhibited by N-ethylmaleimide, was identified as the enzyme responsible for PSGL-1 cleavage.

Conclusions:

  • Downregulation of PSGL-1 on apoptotic monocytes may prevent inappropriate cell clearance, reducing vascular inflammation and proliferation.
  • PSGL-1 depletion on apoptotic microparticles may serve as a molecular switch modulating their thrombogenic potential.

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