Effect of 4-hydroxynonenal, a product of lipid peroxidation, on NK susceptibility of human K562 target cells

4-Hydroxynonenal (HNE) is one of the major breakdown products generated by lipid peroxidation of cellular membranes. The level of lipid peroxidation a nd the concentration of its products are inversely related to the rate of c ell proliferation and directly related to the level of cell differentiation . It has been reported that HNE inhibits DNA synthesis, ornithine decarboxy lase (ODC) activity and c-myc expression in different leukemic cell lines. It has also been demonstrated that HNE inhibits proliferation and induces d ifferentiation in HL60 cell line In the present study the effects of HNE, a t concentrations close to those found in the normal tissues, on the NK susc eptibility of human K562 target cells were analyzed. Repeated treatments at 45 minutes intervals with 1 mu M HNE were performed to maintain the cells in the presence of the aldehyde for 12 hours. The effect of HNE was compare d with that obtained in Haemin-treated cells. HNE causes a strong inhibitio n of cells growth (53% vs. 34% with Haemin) without affecting cell viabilit y. We further investigated the NK susceptibility of K562 cell line upon in vitro treatment with HNE. Cytotoxic activity of mononuclear cells (MNC) fro m peripheral blood of healthy donors was determined by 4 hours Cr-51-releas e assay. The results obtained, expressed in terms of percentage of specific lysis at different E:T ratios and in terms of KC (10 degrees) at the E:T r atio of 50:1, show that HNE treatment of K562 cells leads to a marked reduc tion of susceptibility to NK cells; this decrease is very close to that fou nd in the K562 cells treated with Haemin used as inducer. Similar results w ere obtained using MNC pre-treated with beta-interferon (IFN) as effector c ells. MNC show a reduced capacity to lyse HNE-treated cells also under the enhancing cytolytic effect of IFN. These results are in line with data obta ined with several common inducers of differentiation such as DMSO, retinoic acid or others.