Reversal of lovastatin‐mediated inhibition of natural killer cell cytotoxicity by interleukin 2
- 1 November 1990
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 145 (2), 244-252
- https://doi.org/10.1002/jcp.1041450208
Abstract
The activation of human natural killer (NK) cell cytotoxicity by interleukin 2 (IL-2) is well established, although the biochemical mechanisms ofthis stimulation have not yet been fully delineated. Earlier, we reported that treatment of NK cells with an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase such as compactin or lovastatin significantly abrogates the in vitro killing of a susceptible human erythroleukemic cell line and that this inhibition can be completely reversed by 2 hr of exposure to mevalonate (J. Cell. Physiology 139:550–557, 1989). We report here that 24 hr of treatment with IL-2 also reverses lovastatin inhibition of NK cell function. In addition to natural cytotoxicity, IL-2 also restores chemotactic and antibody dependent cellular cytotoxicity functions to lovastatin-treated cells. IL-2 does not stimulate proliferation of these cells during this time period, nor does it affect the phenotypic composition of the NK cell preparations. Although IL-2 was able to reverse the lovastatin-mediated inhibition of every cell function we examined, it had no effect on the inhibition of cholesterol biosynthesis as measured by [3H]acetate incorporation into non-saponifiable lipids, nor did it stimulate HMG CoA reductase activity. These findings support the hypothesis that there is a non-sterol isoprenoid product which is required for NK cell cytotoxicity and chemotaxis. In addition, the data suggest that IL-2 stimulation of NK cells proceeds by an isoprenoid-independent pathway.This publication has 66 references indexed in Scilit:
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