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7ß-hydroxycholesterol induces natural killer cell death via oxidative lysosomal destabilization
Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
2009 (English)In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 43, no 11, p. 1072-1079Article in journal (Refereed) Published
Abstract [en]

Peripheral natural killer (NK) cells are reduced in patients with coronary artery disease and highly susceptible to apoptosis induced by oxidized lipids including 7beta-hydroxycholesterol (7betaOH) in vitro. The present study aimed to further explore the mechanisms behind 7betaOH-mediated cytotoxicity to human NK cells. Human NK cells were purified and treated with 7betaOH in different concentrations and times. Cell death, lysosomal and mitochondrial permeabilization and reactive oxygen species (ROS) production were then analysed. The 7betaOH induced time and dose dependent apoptosis and necrosis in human NK cells, which was preceded by loss of lysosomal integrity and enhanced ROS production. At later time points, the mitochondrial membrane permeability in 7betaOH-treated cells was significantly increased. The findings indicate that 7betaOH induces human NK cell death through early lysosomal permeabilization and consequent oxidative stress. The data further suggest that 7betaOH may induce immune disturbances in clinical settings such as atherosclerosis.

Place, publisher, year, edition, pages
2009. Vol. 43, no 11, p. 1072-1079
Keywords [en]
Atherosclerosis, cell death, 7β-hydroxycholesterol, lysosomal membrane destabilization, NK cells
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-20992DOI: 10.1080/10715760903176919PubMedID: 19707922OAI: oai:DiVA.org:liu-20992DiVA, id: diva2:240319
Available from: 2009-09-28 Created: 2009-09-28 Last updated: 2017-12-13Bibliographically approved

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Li, WeiYuan, Xi-MingJonasson, Lena

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