Effect of 4-hydroxynonenal, a product of lipid peroxidation, on natural cell mediated cytotoxicity

Lipid peroxidation of cell membrane yields a variety of final products whos e a quantitatively important component is 4-hydroxynonenal (HNE). Previous studies performed in our laboratory suggest that HNE may play a physiologic al role in the control of cellular proliferation and/or differentiation. Th is appears to be further supported by our recent findings showing that pre- treatment of K562 cells with a physiological concentration of HNE leads to a marked reduction of susceptibility to NK cells. The observed regulatory e ffects of HNE on tumor cell growth and susceptibility to natural immune res istance, led Its to try to better understand the immunotoxicological proper ties of this aldehyde. The present study analyses the effects of HNE on NK- mediated cytotoxicity. Treatment of MNC as effector cells with concentratio ns of HNE ranging from 0.001 to 1 mu M for 1h, did not produce noticeable e ffects on NK activity. Therefore, this aldehyde at physiological concentrat ions is able to differentiate tumor cells and to down-regulate target susce ptibility to NK effecters from one side. On the other side, it is nor able to modify the efficiency of the NK function. Moreover; HNE concentrations h igher than 1 mu M showed significant and concentration-dependent inhibition of NK activity. However; this effect is reversible and can be antagonized, at least in part, by treatment of effector cells with HNE in combination w ith beta-interferon.