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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

Negative feedback regulation of activated macrophages via Fas-mediated apoptosis

T Niinobu1, K Fukuo, O Yasuda

  • 1Department of Geriatric Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, Japan.

American Journal of Physiology. Cell Physiology
|July 27, 2000
PubMed

Insights

Activated macrophages release nitric oxide (NO) to induce self-apoptosis via the Fas pathway. This Fas-mediated apoptosis helps regulate and eliminate activated macrophages, preventing excessive inflammation.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Apoptosis is crucial for eliminating activated macrophages.
  • Macrophages play a key role in immune responses and inflammation.

Purpose of the Study:

  • To investigate the role of Fas-mediated apoptosis in the negative feedback regulation of activated macrophages.
  • To elucidate the mechanism by which nitric oxide (NO) induces macrophage apoptosis.

Main Methods:

  • Utilized Fas-Fc chimeric molecules to block Fas ligand (FasL) interaction.
  • Employed a matrix metalloproteinase inhibitor (KB-8301).
  • Analyzed Fas mRNA expression and macrophage apoptosis in Fas-lacking mice.
  • Assessed peroxide production in the presence of a caspase inhibitor.

Main Results:

  • High levels of NO induced apoptosis in activated macrophages.
  • Fas-Fc treatment inhibited NO-induced macrophage apoptosis.
  • NO stimulated the release of soluble FasL, inhibited by KB-8301.
  • NO upregulated Fas mRNA expression.
  • Macrophages from Fas-lacking mice were resistant to NO-induced apoptosis.
  • Caspase inhibition augmented peroxide production, suggesting apoptosis limits macrophage activation.

Conclusions:

  • Fas-mediated apoptosis is a key mechanism for negative feedback regulation of activated macrophages.
  • High NO levels promote Fas-mediated apoptosis, contributing to the elimination and downregulation of activated macrophages.
  • This pathway may be important for controlling inflammation within the vessel wall.

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