期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 39, 期 6, 页码 1456-1465出版社
WILEY
DOI: 10.1002/eji.200838863
关键词
Adhesion molecules; Cytotoxicity; Human; NK cells
类别
资金
- Deutsche Forschungsgemeinschaft [SFB 405, A13]
- Deutsche Krebshilfe
- BMBF (BioFuture)
Inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, commonly referred to as statins, are inhibitors of cholesterol biosynthesis. They are broadly used for treating hypercholesterolemia and for prevention of cardio- and cerebrovascular diseases. Recent publications show that statins also act as immunomodulatory drugs. Here, we show that lipophilic statins inhibit NK-cell degranulation and cytotoxicity. This effect was reversible by addition of substrates of isoprenylation, but not by addition of cholesterol. in NK-target cell conjugates intracellular Ca2+ flux was unaffected by statin treatment. However, statins strongly reduced the amount of conjugate formation between NK and target cells. This inhibition was paralleled by a statin-dependent inhibition of LFA-1-mediated adhesion and a reduction of NK-cell polarization. This demonstrates that statins impair the formation of effector-target cell conjugates resulting in the disruption of early signaling and the loss of NK-cell cytotoxicity.
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