Sensitivity to attack of natural killers depends on integrity of lipid rafts in plasma membrane of transformed cells

被引：0

作者：

Filatova N.A. ^{[1
]}

Chubinskij-Nadezhdin V.I. ^{[1
]}

Ivanov V.A. ^{[1
]}

Morachevskaya E.A. ^{[1
]}

机构：

[1] Institute of Cytology, Russian Academy of Sciences, St. Petersburg

来源：

Cell and Tissue Biology | 2011年 / 5卷 / 1期

基金：

俄罗斯基础研究基金会;

关键词：

alpha-cyclodextrin; cholesterol; human leukemia K562 cells; lipid rafts; methyl-beta-cyclodextrin; natural killer; plasma membrane;

D O I：

10.1134/S1990519X11010068

中图分类号：

学科分类号：

摘要：

This work deals with an analysis of the role of cholesterol-rich lipid microdomains (rafts) in cellular mechanisms of natural immunity and antitumor defense. The lytic action of natural killer (NK) cells was studied depending on the cholesterol content and the state of lipid rafts in the plasma membrane of transformed cells. In this work, the targets were human leukemia K562 cells. For the partial extraction of cholesterol, methyl-beta-cyclodextrin (MbCD), cyclic oligosaccharide selectively binding sterols, was used. A decrease in the cholesterol level after the incubation of cells with MbCD was confirmed by the enzymatic method. Using the 3H-uridine test, the activity of NK (mouse splenocytes) towards the cultivated K562 cells was estimated under different conditions, including those after the cell incubation with MbCD or alpha-cyclodextrin (aCD), a structural MbCD analog that does not bind sterols. The results obtained indicate that a decrease in the cholesterol content in K562 cells (after treatment with MbCD at a concentration of 2. 5 or 5 mM) leads to the complete loss of their sensitivity to the NK lytic action. Most likely, this is caused by a disturbance of the structure of the lipid rafts whose integrity critically depends on the membrane cholesterol level. These conclusions agree with the data on the visualization of the cellular surface changes obtained at the fluorescent labeling of the ganglioside GM1, a marker of the cholesterol-rich lipid microdomains. © 2011 Pleiades Publishing, Ltd.

引用

页码：47 / 53

页数：6

共 43 条

[1]

Ando I., Hoon D.S.B., Suzuki Y., Ganglioside GM2 on the K562 Cell Line Is Recognized As a Target Structure by Human Natural Killer Cells, Int. J. Cancer, 40, pp. 12-17, (1987)

[2]

Bang B., Gniadecki R., Gajkowska R., Disruption of Lipid Rafts Causes Apoptotic Cell Death in HaCaT Keratinocytes, Exp. Dermatol., 14, pp. 266-272, (2005)

[3]

Bowlin T.L., Rosenberger A., Stemerick D., Edwards M.L., Potentiation of Natural Killer Cell Activity and Tumor Immunity by Diacetylputrescine, Cancer Res., 50, pp. 5460-5463, (1990)

[4]

Brown D.A., Lipid Rafts, Detergent-Resistant Membranes, and Raft Targeting Signals, Am. J. Physiol., 21, pp. 430-439, (2006)

[5]

Brown M.H., Boles K., van der Merwe P.A., Kumar V., Mathew P.A., Barclay A.N., 2B4, the Natural Killer and T Cell Immunoglobulin Superfamily Surface Protein, Is a Ligand for CD48, J. Exp. Med., 188, pp. 2083-2090, (1998)

[6]

Brown D.A., London E., Structure and Function of Sphingolipid- and Cholesterol-Rich Membrane Rafts, J. Biol. Chem., 275, pp. 17221-17224, (2000)

[7]

Brown D.A., Rose J.K., Sorting of GPI-Anchored Proteins to Glycolipid-Enriched Membrane Subdomains During Transport to the Apical Cell Surface, Cell, 68, pp. 533-544, (1992)

[8]

Byfield F.J., Aranda-Espinoza H., Romanenko V.G., Rothblat G.H., Levitan I., Cholesterol Depletion Increases Membrane Stiffness of Aortic Endothelial Cells, Biophys. J., 87, pp. 3336-3343, (2004)

[9]

Chichili G.R., Rodgers W., Cytoskeleton-Membrane Interactions in Membrane Raft Structure, Cell Mol. Life Sci., 66, pp. 2319-2328, (2009)

[10]

Christian A.E., Haynes M.P., Phillips M.C., Rothblat G.H., Use of Cyclodextrins for Manipulating Cellular Cholesterol Content, J. Lipid Res., 38, pp. 2264-2272, (1997)

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