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A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation
12:55

A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation

Published on: December 9, 2021

Endothelium down-regulates Fas, TNF, and TRAIL-induced neutrophil apoptosis

Steven D Tennenberg1, Raphaela Finkenauer, Tao Wang

  • 1Department of Surgery, John D. Dingell Veterans Affairs Medical Center, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. steven.tennenberg@med.va.gov

Surgical Infections
|April 17, 2003
PubMed
Abstract

Insights

Endothelial cells reduce neutrophil apoptosis via Fas, TNF, and TRAIL pathways. This interaction, crucial for resolving inflammation, does not involve caspase 3 activity changes.

Area of Science:

  • Immunology
  • Cell Biology
  • Inflammation Research

Background:

  • Neutrophil (PMN) apoptosis is critical for resolving inflammation and regulating PMN lifespan.
  • Endothelial cell contact was previously shown to reduce spontaneous PMN apoptosis.
  • This study investigates endothelial effects on mediator-induced PMN apoptosis via key apoptotic pathways.

Purpose of the Study:

  • To determine if endothelial cells down-regulate PMN apoptosis induced by Fas, TNF, and TRAIL.
  • To explore the mechanism of endothelial-mediated apoptosis regulation in neutrophils.

Main Methods:

  • Human coronary artery endothelial cells (HCAECs) were co-cultured with primary neutrophils (PMNs).
  • PMNs were stimulated with agonistic anti-Fas IgM, TNF, or TRAIL after co-culture.
  • Apoptosis was assessed using fluorescent microscopy, and Caspase 3 activity was measured.

Main Results:

  • Endothelial co-culture significantly decreased PMN apoptosis following stimulation with anti-Fas IgM, TNF, and TRAIL.
  • Co-culture increased the percentage of viable neutrophils and decreased apoptotic neutrophils.
  • Endothelial co-culture did not alter PMN Caspase 3 activity.

Conclusions:

  • Endothelial contact down-regulates Fas, TNF, and TRAIL-mediated PMN apoptosis after 4 hours of co-culture.
  • The mechanism may involve a defect in a common distal pathway, not Caspase 3.
  • Endothelial cells play a significant role in modulating neutrophil apoptosis during inflammation resolution.

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