7beta-hydroxycholesterol induces natural killer cell death via oxidative lysosomal destabilization

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Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
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Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells

Published on: February 22, 2020

Wei Li1, Henrik Johnson, Xi-Ming Yuan

  • 1Pharmacology, Department of Medical and Health Sciences, Linköping University, 581 85 Linköping, Sweden. weili@imv.liu.se

Free Radical Research
|August 27, 2009
PubMed

Insights

Oxidized lipids like 7beta-hydroxycholesterol (7betaOH) trigger natural killer (NK) cell death in coronary artery disease patients. This occurs via lysosomal damage and oxidative stress, impacting immune function in atherosclerosis.

Area of Science:

  • Immunology
  • Cardiovascular Science
  • Cell Biology

Background:

  • Peripheral natural killer (NK) cells are reduced in coronary artery disease (CAD).
  • Oxidized lipids, including 7beta-hydroxycholesterol (7betaOH), induce NK cell apoptosis in vitro.
  • Mechanisms of 7betaOH-induced cytotoxicity to human NK cells require further elucidation.

Purpose of the Study:

  • To investigate the mechanisms underlying 7betaOH-mediated cytotoxicity to human NK cells.
  • To determine the effects of 7betaOH on NK cell viability, lysosomal and mitochondrial integrity, and reactive oxygen species (ROS) production.

Main Methods:

  • Human NK cells were purified.
  • Cells were treated with varying concentrations and durations of 7betaOH.
  • Assays were performed to analyze cell death, lysosomal and mitochondrial permeabilization, and ROS production.

Main Results:

  • 7betaOH induced time- and dose-dependent apoptosis and necrosis in human NK cells.
  • Loss of lysosomal integrity and increased ROS production preceded cell death.
  • Mitochondrial membrane permeability increased significantly at later time points.

Conclusions:

  • 7betaOH induces human NK cell death through early lysosomal permeabilization and subsequent oxidative stress.
  • These findings suggest 7betaOH may contribute to immune disturbances in atherosclerosis.
  • Understanding this mechanism is crucial for managing immune function in cardiovascular disease.

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